Vaccines Have Serious Side Effects

The Revised Authoritative Guide To Vaccine Legal Exemptions

Comprehensive, authoritative information about vaccine exemptions you can trust, from Alan Phillips, J.D., a leading vaccine rights attorney with years of experience helping clients throughout the U.S. legally avoid vaccines in a wide variety of vaccine-refusal settings. Critical details for parents, students, immigrants, healthcare employees, military personnel and contractors, agencies, attorneys and clientsvirtually anyone concerned with legally avoiding vaccines in the United States. This Guide provides and explains: Important background information about the legal system; How state and federal statutes, regulations, constitutions and legal precedent interact to define the boundaries of your legal exemption rights; How to deal with local authorities and to avoid mistakes that cost others their exemption; Where legal technicalities and practical reality differand what to do about it; Read more here...

The Revised Authoritative Guide To Vaccine Legal Exemptions Summary


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The Similarity Between Sex And Vaccination

At this point the alert know-it-alls among you will be seething with impatience at my neglect of the immune system. The normal way to fight a disease, you may point out, is not to have sex but to produce antibodies, by vaccination or whatever. The immune system is a fairly recent invention in geological terms. It started in the reptiles perhaps 300 million years ago. Frogs, fish, insects, lobsters, snails, and water fleas do not have immune systems. Even so, there is now an ingenious theory that marries the immune system with sex in an overarching Red Queen hypothesis. Hans Bremermann of the University of California at Berkeley is its author, and he makes a fascinating case for the interdependence of the two The immune system, he points out, would not work without sex.

Influenza vaccine 255

Influenza vaccine A sterile suspension of killed influenza virus types A and B, either individually or combined. Commonly known as a flu shot. The influenza vaccine varies in its effectiveness, depending on whether the strain of the virus in the vaccine is related to the virus that is causing the influenza. The effectiveness of the vaccine changes annually with every flu season, since the prevalent types of flu are different each year. In most years, however, the vaccine probably prevents illness in about 70 percent of the people who receive it, and those who become infected despite having been vaccinated usually have less severe symptoms. Influenza does not seem to be unusually common or severe in people with HIV infection. The only problem specific to people with HIV infection is that the symptoms of influenza can be confused with the symptoms of other disorders, such as

Control by vaccination

In essence, the simple epidemic extinguishes itself by reducing its supply of susceptibles below 1 R0. The same threshold also applies to control of immunizing pathogens by vaccinating with an inactivated or attenuated pathogen (Anderson and May, 1991) reducing the proportion of susceptibles below 1 R0 will keep R below unity and prevent invasion of the infection. Note that the resulting critical proportion of susceptibles that require vaccination to prevent an epidemic (pc 1 1 R0) is less than unity this reflects the concept of herd immunity in which not all susceptible individuals in a population need to be protected to prevent a large-scale epidemic logistical constraints then determine whether this level of vaccination can be achieved.

National Childhood Vaccine Injury Act of 1986

A vaccine safety and compensation system established by Congress in 1986 to create a no-fault compensation alternative to suing vaccine manufacturers and providers for citizens injured or killed by vaccines. The act also created safety provisions to help educate the public about vaccine benefits and risks, and to require doctors to report adverse events after vaccination as well as keep records on vaccines administered and health problems which occur following vaccination. Finally, the act also created incentives for the production of safer vaccines. For any injuries or deaths before October 1, 1988 (no matter how long ago the injury occurred), a citizen may choose to pursue a lawsuit. For injuries or deaths occurring after that date, a citizen is required to apply for federal compensation before pursuing a lawsuit. The government will offer to pay up to 250,000 for a vaccine-associated death, or will offer to pay for all past and future unreimbursed medical expenses, custodial and...

National Vaccine Injury Compensation Program

The NATIONAL CHILDHOOD VACCINE INJURY ACT of 1986 (PL 99-660). The program is designed to ensure an adequate supply of vaccines, stabilize vaccine costs, and maintain an efficient way to help children injured by childhood vaccines. The program, which went into effect October 1, 1988, is a no-fault alternative to the traditional tort system for resolving vaccine injury claims. Since its inception, the Vaccine Injury Compensation Program (VICP) has helped stabilize the U.S. vaccine market by providing liability protection to both vaccine companies and health-care providers, by encouraging research and development of new and safer vaccines, and by allowing a quicker and less adversarial alternative to lawsuits. The VICP covers all vaccines recommended by the Centers for Disease Control and Prevention for routine administration to children In the early 1980s reports of harmful side effects after the DTP (diphtheria, tetanus, pertussis) vaccine posed major liability concerns for vaccine...

Tumor angiogenesis vaccines

In addition to discovering more potent angiogenic inhibitors, new approaches are on the horizon for antiangiogenic molecular therapy. Vaccines toward tumor angiogenesis are now being developed with purified proteins (8,10) or with whole-cell endothelial extracts from tumors (15). In one study, fixed xenogeneic whole endothelial cells were effective as a vaccine in protecting against tumor growth, inducing regression of established tumors, and prolonging survival of tumor-bearing mice. In three other studies, purified angiogenic receptors were used as antigens to develop a tumor neovascularization vaccine. Vaccination with FGFR-1 (8) and VEGR-2 (10,101) effectively induced antitumor immunity and activity in vivo. There was marked tumor reduction and prolonged survival with few side effects in the vaccinated animals in all three studies. Although these results in preclinical models have been encouraging, the success of active immunization will depend on specificity toward tumor...

Prevention And Vaccine

No vaccine is yet available and the only effective prevention at present is education about the ways of transmission, systematic testing of blood donors and the use of condoms. However, an important reduction of transmission from mother to child has been achieved by treatment with AZT of the mother at the end of pregnancy and at the time of delivery and of A complete control of the AIDS epidemic cannot be achieved without the availability of a protective vaccine. Although the use of whole virus or whole surface glycoproteins has been disappointing, there are new promising approaches based on the use of DNA, mucosal adjuvants and live vectors, internal and regulatory proteins, and conserved parts of the surface glycoproteins. The efficacy trials of candidate vaccine in large populations will raise important logistic and ethical issues difficult to solve, unless an important international mobilization greater than that achieved for vaccinal eradication of poliomyelitis, is achieved.

Prophylactic vaccine See vaccine

Prophylaxis Any intervention intended to preserve health and prevent the initial occurrence (primary prophylaxis) or the recurrence (secondary prophylaxis) of a disease. The intervention may be in the form of a drug (such as a vaccine) or other treatment or the use of a device (such as a condom).

Toward Vaccine Prevention

Considering that the protective immunity against Shigella infection is essentially serotype-specific, the protective capacity of any Shigella vaccine candidate will depend greatly on the representation of serotypes incorporated in the vaccine and the epidemiological importance of these respective serotypes in the area. This emphasizes the need for evaluation of the disease burden and of the representation of serotypes in any area where such vaccine candidates are to be studied (Clemens et al., 1999). Initial attempts at immunizing against shigellosis were based on whole-cell killed preparations administered parenterally. The complete failure that followed this approach led to the concept that parenteral immunization could not successfully protect against shigellosis. For a disease that remained local, mucosal immunization with live attenuated oral vaccine candidates was a better option. Initial attempts in the mid-sixties using multiple oral doses of streptomycin-dependent (SmD)...

Immunology relevant to vaccines

Vaccines are used to mimic the body's response to natural infection, so that an antigen-specific immunological memory is induced in the body that will protect it from subsequent exposure to that antigen. A brief background to relevant basic immunology is provided so that this chapter is understandable and useful to readers with varied backgrounds. The undesirable aspects of immunogenicity of proteins used as therapeutic agents are discussed separately in Chapter 1 . The most important cells involved in immunity are the white blood cells or leukocytes, which include phagocytes, natural killer (NK) cells (part of the innate immune system providing the first line of defense), and lymphocytes (which mediate adaptive immunity). The NK cells are activated by interferons (IFNs) produced by virally infected cells and sometimes by lymphocytes. NK cells, along with cytokines, provide a first line of defense that involves nonspecific immune response initiated within minutes of exposure to an...

Immune responses to vaccines

Immune system and has its primary immunoglobulin subtype as IgA rather than IgG. A well-characterized mucosa-associated lymphoid tissue (MALT) is the PP, a gut-associated lymphoid tissue (GALT) in the small intestine.29 Other lymphoid tissues include the bronchus-associated lymphoid tissue (BALT) and the nasal-associated lymphoid tissue (NALT). Many earlier studies measured effectiveness of vaccination by simple antibody measurement followed by challenge experiments. However, with increasing knowledge of immunology and availability of specialty reagents, it is now possible to evaluate the immune response more thoroughly. Measurements can include immunokinetics, duration of protection, and type of response, such as the antibody subclass-, cyto-kine-, and cell-mediated immune responses.30 Standard vaccines based on killed pathogens or antigens do not enter the cells and thus mainly produce humoral responses. The protection often wears off after some time, and thus booster shots are...

Delivery approaches for administration of vaccines

Some of the important delivery approaches for administration of vaccines are discussed in this section. Electroporation has also been investigated for delivery of peptide- protein-based antigens. It has been reported to be a promising technique for nonadjuvanted skin immunization, especially for low molecular weight, weakly immunogenic antigens. However, this study in mice reported that the mice experienced a significant muscle contraction during the application of the electroporation voltage.66 Formulation and stability considerations are also important for delivery approaches. The optimal formulation will need to be specifically developed for a particular antigen, but other factors such as the route of administration will also have to be taken into consideration. An understanding of the role of various antigens of the pathogen in infection and immunity is required and may allow for formulation of an appropriate cocktail of epitopes in some cases to induce a broad range of protective...

Rhabdovirus Vector Vaccines

RV nucleocapsids have been shown to function as an exogenous superantigen specific for V 8- and V 6 T-cell-receptors (TCR) in humans and mice, respectively (Lafon et al. 1992 Lafon et al. 1994). Superantigens usually bind directly to class II major histocompatibility proteins and elicit a powerful proliferative response of T lymphocytes. In mice bearing the V 6 TCR, RV nucleocapsids were able to stimulate both T- and B-cell-specific immune responses against the co-administered influenza virus HA antigene (Astoul et al. 1996), demonstrating the high potential of RV as a vaccine vector with intrinsic adjuvant function. While the remarkable immunogenicity of rhabdovirus particles is perfect in terms of eliciting initial immune responses, it may preclude multiple use of the same vector for boosting in heterologous vaccine applications. This, however, can be circumvented by using vectors with different envelope proteins, as demonstrated by the group of J. Rose who produced a series of VSV...

Pneumococcal conjugate vaccine PCV A new

Vaccine approved in 2000 to prevent invasive pneumococcal diseases in infants and toddlers, diseases that can cause brain damage and, in rare cases, death. The pneumococcal conjugate vaccine (PCV) is not indicated for use in adults or as a substitute for other approved pneumococcal polysac-charide vaccines approved for high-risk children over age two. The previous pneumococcal vaccine (PPV) was not recommended for use in children under age two, who contract the most serious infections from this bacteria. The new PCV vaccine (Prevnar) protects against the organism Streptococcus pneumoniae (also known as pneumococcus), the leading cause of pneumonia, sinusitis, ear infection, and meningitis. It has been added to the recommended schedule of childhood immunizations. It is given to infants as a series of four inoculations administered at age two, four, six, and 12 to 15 months of age. If a child cannot begin the vaccine at two months, parents should discuss alternative schedules with their...

Development Of Vaccines And Passive Immunotherapy Against Sars Coronavirus Using Mouse And Scidpblhu Mouse Models

We have investigated novel vaccines strategies against severe acute respiratory syndrome (SARS) CoV infection using cDNA constructs encoding the structural antigens spike (S), membrane (M), envelope (E), or nucleocapsid (N) protein, derived from SARS CoV (strain HKU39849, TW1, or FFM-1). As SARS-CoV is thought to infect the alveolar epithelial cell of the lung,in the present study, a type II alveolar epithelial cell clone, T7, was used to analyze the mechanism of CTL against SARS CoV membrane antigens. Mice vaccinated with SARS CoV (N) DNA or (M) DNA using pcDNA 3.1(+) plasmid vector showed T-cell immune responses (CTL induction and proliferation) against type II alveolar epithelial cells (T7) transfected with SARS (N) or (M) DNA, respectively. To determine whether these DNA vaccines could induce T-cell immune responses in humans as well as in mice, SCID-PBL hu mice were immunized with these DNA vaccines. PBL from healthy human volunteers were administered i.p. into IL-2 receptor...

Going Bananas with Vaccines

In the late 1700s, an English physician, Edward Jenner, administered the world's first medical vaccine. Using a needle soaked in fluid from the open sore of a milkmaid with cowpox (a bovine version of smallpox that produces only mild symptoms in humans), he scratched a farmboy's arm. Upon later exposure to smallpox virus, the boy successfully resisted this otherwise deadly disease. From Jenner's experiment came not only the vaccine concept, but also the word itself, which derives from the Latin root vacca, meaning cow. In general, vaccines are harmless biological agents prepared from pathogens (disease-causing organisms, typically bacteria, viruses, fungi, or other parasites) that, when delivered to a patient, elicit immune responses providing the patient with protection against the disease. The body's immunological memory varies among vaccines. Some vaccines, such as those for mumps and rubella, offer lifetime immunity, whereas others, such as for tetanus and smallpox, must be...

The Vaccination Process

Injecting vaccine Vaccine' fever in the 1920s, and Jonas Salk and Albert Sabin produced polio vaccines in the 1950s. Today, there are vaccines for mumps, rubella, measles, tetanus, chicken pox, flu, and other once dangerous diseases. But there are many viral infections that the medical community cannot prevent with an injection. For example, there are too many strains of the common cold to create an effective vaccine, and other viruses mutate too quickly. A virus can alter its outer protein coat so that antibodies and vaccines that once worked on the virus are no longer effective. Even


Active immunization is provided by a vaccination that stimulates the immune system to make protective antibodies that protect you for life. The chicken pox vaccine Varivax is made from a The development of a vaccine against the disease has been studied and used in clinical trials with children and adults in the United States since the early 1980s it has been used in Japan for some time. It protects 70 to 90 percent of children but does not work well on adults. In March 1995 the U.S. Food and Drug Administration licensed the vaccine for general use the American Academy of Pediatrics has recommended the vaccine for all children and teenagers. Children younger than 12 require one dose children 13 and over require two shots four to eight weeks apart. Not all physicians agree on the benefits of the vaccine for healthy children, however. While proponents of the vaccine point out that suffering children and parents' considerable lost work time are good reasons to use the vaccine, some...

The First Vaccine

One boy who was inoculated was eight-year-old Edward Jenner. He survived the painful procedure and grew up to be a country doctor whose keen observations led to the first vaccinations. Jenner went on to repeat his experiments and published his results, calling his technique vaccination and the matter taken from the cowpox sore a vaccine (derived from vacca, the Latin word for cow). In a letter written to a friend, Jenner predicted, The annihilation of smallpox the most dreadful scourge of the human race will be the final result of this practice.16 Jenner would never know how accurate his prediction would become. He also would never know how his vaccine worked or even what kind of organism he was actually fighting against. That information would not come for many more years.

Rabies Vaccine

Louis Pasteur had created a successful vaccine for chickens, another for sheep, and he had been experimenting on a rabies vaccine for dogs, but he had not developed a safe vaccine for humans. But that did not matter to the mother of nine-year-old Joseph Meister, who took her son to Pasteur's office in 1885. A mad dog had bitten Joseph. Rabies is a horrible disease that infects only mammals. The virus attacks the nervous system and infects the brain, causing a difficult and painful death. Pasteur knew that a weakened germ worked as a vaccine against other diseases in animals and believed that a similar treatment for humans should work against rabies. He injected Joseph with the weakened vaccine and increased the dose daily. After fourteen days Joseph Meister was stronger and had made history. He became the first person to survive rabies.


The development of controlled release vaccines is receiving increasing attention. Immunization is discussed in detail in Chapter 10 some brief comments on parenteral vaccines are made here. Normally, immunization requires multiple injections, and dropout rates from the first to the second dose can be as high as 70 in developing countries. A controlled release vaccine may deliver the antigen to achieve a long-lasting effect following a single injection. Development of a pulsatile release pattern may also allow a single injection to provide both the primary and booster immunizations.50 Many antigens are often only weakly immunogenic, and the use of adjuvants may be required to enhance the antibody response. Currently, aluminum salts are used as adjuvants. Particulate carriers based on synthetic polymers can also act as adjuvants in addition to providing controlled release. Adsorption and incorporation of influenza virus antigen into poly(methyl methacrylate) nanoparticles has been shown...

Polio vaccine

Until recently, the live oral polio vaccine (OPV) had been recommended for most children because while both vaccines provide immunity to polio, OPV was better at keeping the disease from spreading to other people. However, for a few people (about one in 2.4 million), OPV actually causes polio. Since there is now virtually no chance of getting polio in the United States, experts decided that using oral polio vaccine is no longer worth the chance of infecting five to 15 American children each year. The killed virus polio shot (IPV) never causes polio and is not known to cause any side effects other than minor local pain and redness.

Vaccine adjuvants

Adjuvants are substances that nonspecifically enhance the immune response to antigens. Antibody responses to antigens in adjuvants are greater and more prolonged and frequently consist of different classes to the response obtained without adjuvants. Conventional killed or attenuated vaccines or recombinant subunit vaccines typically used today are generally administered with adjuvants to elicit effective immune responses. Many of these adjuvants can cause tissue reactions currently, only Alum is licensed in the United States for human use. When Alum is used, the antigen binds to the aluminum hydroxide or aluminum sulfate and forms a macroscopic suspension. Alum is somewhat effective in potentiating humoral immunity but does not generally elicit CD8+ T-cell-mediated responses. The amount of aluminum in biological products, including vaccines, is limited to 0.85 mg dose. Aluminum adjuvants have been used for decades and are generally safe nevertheless, they can cause local reactions...

Subunit vaccines

The newer-generation vaccines such as subunit, recombinant, and synthetic vaccines have several advantages with respect to formulation (e.g., higher purity, easier quality control), but unfortunately they tend to be poorly immunogenic compared to live attenuated vaccines. Therefore, the need to develop alternate adjuvants becomes more critical. Generally, proteins would be more immunogenic than peptides as they would have a larger number of epitopes and may be more stable in vivo. Nevertheless, they are still poorly immunogenic compared to conventional killed or attenuated vaccines. Another very promising strategy to produce very immunogenic purified proteins is through the use of viruslike particles (VLPs). Structural proteins derived from a variety of viruses can spontaneously assemble into VLPs. These particles can trigger potent humoral responses and even cellular responses as they can be captured by antigen-presenting cells because of their size and structure. Chimeric VLPs...

DNA vaccines

A third-generation approach termed DNA immunization has also been under investigation over the last few years. It makes use of plasmids, which are the small rings of double-stranded DNA derived from bacteria. These plasmids are modified to carry genes that code for the antigenic protein made by a pathogen. DNA vaccination then refers to the direct introduction of plasmid DNA into body tissues, where it is able to express an antigenic protein and raise immune responses. This innovative approach to immunization is promising for development of needed vaccines19-21 but still is in relatively early developmental stages. The antigen encoded in the plasmid, with the proper regulatory sequences, transfects the cells in vivo to express the antigen (using the biosynthetic machinery of the host), which in turn leads to induction of an immune response. The plasmid excludes genes that may enable the pathogen to reconstitute itself and cause disease.

BEF Vaccines

Several forms of live-attenuated, inactivated, subunit and recombinant BEF vaccines have been reported. The efficacy and longevity of protection has been variable. Vaccines manufactured in South Africa, Japan, China, Taiwan and Australia have been used in the field for BEF prophylaxis. Live-attenuated vaccines have been produced by serial passage of BEFV in suckling mice and or in cell cultures (Tzipori and Spradbrow 1973,1978 Theodoridis et al. 1973a Spradbrow 1975 Vanselow et al. 1995). In general, live vaccines have been administered in combination with adjuvants (including Freund's complete or incomplete adjuvant, dextran sulphate, aluminium hydroxide or Quil A). It has been reported that Quil A and aluminium hydroxide gel adjuvants inactivate up to 99 of BEFV infectivity (Vanselow et al. 1985). However, it is also known that Quil A can cause aggregation of BEFV particles and that, while the apparent infectivity of high-titre BEFV preparations was clearly reduced following...

Adhesins of Haemophilus influenzae

Haemophilus influenzae is a common pathogen of the human respiratory tract. Isolates of H. influenzae can be divided into encapsulated and nonencapsulated, or nontypable, forms. Prior to the use of H. influenzae conjugate vaccines, capsulated strains of H. influenzae were the primary cause of childhood bacterial meningitis and a major cause of other bacteremic diseases in children. Vaccines effective against nontypable strains have not yet been developed and these strains remain important human pathogens, causing pneumonia, otitis media, sinusitis, and bronchitis. Several

Preface to Second Edition

A new chapter on recombinant protein subunit vaccines and their delivery systems has been added. The focus of this chapter is on recombinant protein-based subunit vaccines as that fits better with the overall scope of this book, especially because many of the products in development will have a therapeutic focus. Since the publication of the first edition, several changes in regulatory considerations have also taken place, including the abolition of the Establishment license and reorganizations within the Food and Drug Administration relevant to biologics these are briefly discussed. In addition, the Process Analytical Technology (PAT) initiative as relevant to proteins is briefly discussed, and other relevant topics, such as statistical design of experiments and well-characterized biologicals, have been added. The discussion on lyophilization has been expanded as this is an important area that needs thorough understanding of several concepts and an awareness of the latest knowledge...

Basic Scientific Discovery and Application to New Drug Development

In an apparent attempt to determine whether the American taxpayer is getting fair benefits from research sponsored by the federal government, the Joint Economic Committee of the U.S. Senate (for history see Ref. 7) has been considering this question. Historically, basic research has been funded by the NIH and various philanthropic foundations to discover new concepts and mechanisms of bodily function, in addition to training scientists. The role of industry has been to apply the basic research findings to specific treatments or prevention of disease. This is the appropriate manner in which to proceed. The industry cannot afford to conduct sufficient basic research on new complicated biological processes in addition to discovering new drugs or vaccines. The government does not have the money, time, or required number of experts to discover and develop new drugs.

Recombinant DNA technology

Biopharming can also be used to produce transgenic crops that can potentially produce genetically engineered molecules, including human antibodies, more cheaply compared to fermentation.1011 Vaccines expressed in plants could potentially be used for oral immunization in this regard, the

AIDS Drug Assistance Program

Peter Duesberg has written many books and articles on his theories that state that illegal drug use leads to AIDS. He has reportedly had himself injected with HIV to prove it does not cause AIDS. San Francisco ACT-uP (not part of the nationwide ACT-uP network) holds that HIV does not cause AIDS and that HIV medications are the culprit in killing people. President Thabo Mbeki of South Africa publicly doubts whether AIDS is caused by HIV and suggests it is the result of whites wanting to kill black Africans. Boyd Graves, a lawyer from California believes he has uncovered proof that HIV is derived from research done in the united States with the Visna virus from sheep. He believes it is part of a continuing eugenics program the united States government funded through the Special Virus Cancer Program, which created the virus and injected it in humans through hepatitis B vaccines tested in gay and African populations. Results of an official government investigation can be found on the...

Prospects for Prevention and Treatment

The identification of a human tumor virus immediately suggests strategies for tumor prevention and control. Public heath measures can be instituted to protect the population from exposure or to identify carriers or people at elevated risk of cancer. Successful examples of this approach are the elimination of HBV and HCV from the blood supply and the use of Pap screening to identify women with HPV-induced cervical dysplasia. In a more recent example, maternal-to-infant transmission of HTLV-1 is reduced if carrier mothers refrain from breast-feeding (Hino et al., 1997). Another well-established modality to control viral infection is vaccination. An effective hepatitis B vaccine is already reducing the incidence of chronic hepatitis B virus infection and hepatocellular carcinoma (Huang and Lin, 2000), and on the basis of clinical trials demonstrating protection against persistent high-risk HPV infection and the development of precancerous lesions, HPV vaccines were recently approved for...

Achievement And Disappointment

The health of the American people at the beginning of the twenty-first century would astonish those living in 1900. By every measure, we are healthier, live longer, and enjoy lives that are less likely to be marked by injuries, ill health, or premature death. In the past century, infant mortality declined and life expectancy increased (DHHS, 2002). Vaccines and antibiotics made once life-threatening ailments preventable or less serious and homes, workplaces, roads, and automobiles became safer. In addition to the many health achievements facilitated by public health1 efforts such as sanitation and immunization, unparalleled medical advances and national investment in health care also have contributed to improvements in health outcomes. Roughly 13 percent of our gross domestic product about 1.3 trillion in 2000, which represents a higher percentage than that of any other major industrialized nation goes toward health-related expenditures (DHHS, 2001 Levit et al., 2002).

The foundations of goalbased thinking

Out of 724 experimental persons, 154 died in the typhus experiments . But these 154 deaths have to be compared with the 15,000 who died of typhus every day in the camps for Soviet prisoners of war, and the innumerable deaths from typhus among the civilian population of the occupied eastern territories and the German troops. This enormous number of deaths led to the absolute necessity of having effective vaccines against typhus in sufficient quantity. (From the Nazi doctors' defence speeches at the Nuremberg Trials, 1947 p. 1017)

Antihemophilic factor A See factor viii

Anti-idiotype antibody A vaccine strategy that is being used in HIV vaccine research. Antibody molecules can assume almost any shape at all. Scientists therefore can take an antibody to the HIV antigen and make copies of it. Then you have an antibody that resembles the HIV antigen. These antibodies are injected into an animal, and that animal's immune system responds by making antibodies to the antibodies. The way this process works for vaccine research is that these new antibodies (known as the anti-idiotype) in the animal are nearly identical to the original antigen (HIV). Giving these anti-idiotype antibodies to humans should allow their immune system to produce antibodies that fight off what resembles an HIV antigen, but in reality is a harmless antigen. It should induce this immune response so the body is protected against invasion by antigens that resemble HIV. This method works in theory on humans and has worked in animals for a variety of viruses, including HBV, rabies,...

Regulatory aspects of biotechnologyderived drugs

Trative point of view because it determines which center of FDA will review the product. Until recently, drugs were regulated under the Food, Drug, and Cosmetic (FD& C) Act biologics are controlled by the Public Health Services (PHS) Act and handled by the Center for Biologics Evaluation and Research (CBER). Under a 2003 reorganization within the FDA, well-characterized biologics will now be handled by the Center for Drug Evaluation and Research (CDER). However, CBER will continue to review blood products and vaccines and evaluate gene therapy products as and when they become available. This reorganization is expected to shorten review times for well-characterized biologics and make the review process more similar to that for traditional conventional drug molecules.

Pharmacoeconomics and the regulatory process

Tech's Activase (tPA) was criticized in the media when first approved because it was much more expensive than its competing product, streptokinase. In addition, the insurance industry and ethical and legal issues are involved in product pricing. Vaccines, therapeutics, and certain diagnostics face the risk of product liability suits. Biotechnology companies may seek liability insurance and recover the costs in pricing.105 Pharmacoeconomics or, more broadly, outcomes research considers the value for money for medications, including considerations of efficacy, effectiveness, and efficiency.106

Bacterial culture See culture

Bacterial pneumonia An inflammation of the lungs caused by bacteria. Although Pneumocystis carinii pneumonia (PCP) is more widely associated with AIDS, bacterial pneumonia also occurs frequently among HIV-infected persons. Community-acquired bacterial infections of all sorts often affect persons with HIV, both women and men. Bacterial pneumonia is also common in pregnancy and may be more common in HIV-positive pregnant women. Symptoms of bacterial pneumonia include fever, wet cough, and chest pain. Some infections are easily treated with standard oral or intravenous antibiotics, while some lead to life-threatening complications. pneumococcal vaccination (along with annual influenza vaccination) has been recommended for people with HIV disease with more than 200 T4 cells, although its effectiveness in HIV disease is unknown. other strategies for dealing with persons at risk include cessation of smoking, the use of trimethoprim-sulfamethoxazole, immunoglobulin therapy, and antimicrobial...

Australian Bat Lyssavirus A Recently Discovered New Rhabdovirus

Abstract Australian bat lyssavirus (ABLV), first identified in 1996, has been associated with two human fatalities. ABLV is genetically and serologically distinct from, but is closely related to, classical rabies. It has a bullet-shaped morphology by electron microscopy. There are two strains of ABLV known one circulates in frugivorous bats, sub-order Megachiroptera, and the other circulates in the smaller, mainly insectivorous bats, sub-order Microchiroptera. Each strain has been associated with one human fatality. Surveillance indicates infected bats are widespread at a low frequency on the Australian mainland. It is unclear how long ABLV has been present in Australia, although molecular clock studies suggest the two strains separated 950 or 1,700 years ago based on synonymous or non-synonymous nucleotide changes, respectively. Recent serological surveys suggest a closely related virus may exist in the Philippines. Due to demonstrated cross-protection in mice, rabies vaccine is used...

Microbial Factories for Pharmaceutical Drugs

The following thumbnail history of microbiology highlights the fact that our knowledge of microbes and their signal role in human health is remarkably recent. In 1836, the German physiologist Theodor Schwann attributed processes of putrefaction and fermentation to microorganisms, a radical notion that the French biochemist Louis Pasteur experimentally confirmed in the 1860s. In 1882, the German Robert Koch developed a method to isolate pure bacterial cultures from the ill and pinpointed the tuberculosis germ as the first known microbe to cause a human sickness. In 1885, the English surgeon Joseph Lister pioneered the use of microbial disinfectants during surgery, thereby profoundly lowering patient death rates. In that same year, Pasteur formally added vaccination to our medicine bag when he successfully treated a nine-year-old Alsatian boy for rabies. In 1892, the Russian Dmitri Ivanovski discovered viruses, even tinier disease agents. In 1917, phage viruses (which infect bacteria)...

Calcium channel blocker See calcium entry

Canarypox A virus that infects birds and is used as a live vector for HIV vaccines. It can carry a large quantity of foreign genes. Small studies with a canarypox-based vaccine combination have been conducted by a variety of governmental agencies, including the National Institutes of Health (NIH). Disappointing results impacted the government's plans to launch a large international 11,000-person, 80-million trial of an HIV vaccine in 2003. Another large trial was slated to start in Thailand in 2002 responsibility for this trial would be shared by the NIH and the Royal Thai Army. This trial is designed to see whether the canarypox combination can cut HIV infection rates in half. Although proving that it would be terrific, researchers caution that the problems start if some smaller, ambiguous degree of protection is reported. In theory, even a modestly protective vaccine could have a significant impact on the pace of the epidemic

Reference Interval SI Units

These results were discussed with the patient. He was interested in pursuing treatment. The patient was advised to stop drinking and return to the clinic after he had completed 6 months of complete sobriety. A prescription was written for vitamin B12 1000 mg subcutaneously once a month for 4 months, folic acid 1 mg daily for 30 days, and thiamine 100 mg daily for 30 days. He also received his first dose of hepatitis A and B vaccine and was instructed to complete the series.

Serological Characteristics

The ability of rabies immune serum to neutralize virus infection is used to distinguish between rabies and rabies-related viruses (Schneider et al. 1973). Rabies immune sera neutralizes both Pteropus and Saccolaimus ABLV strains using the rapid fluorescent focus inhibition test (RFFIT) (Fraser et al. 1996 Hanlon et al. 2001). Hence, by definition, ABLV is a serotype 1 lyssavirus. However, by monoclonal antibody reactivity, both ABLV strains have similar but distinctly different serological profiles to classical rabies (Fraser et al. 1996 Gould et al. 1988,2002 Hooper et al. 1997). Using a Centers for Disease Control (CDC) panel of nucleoprotein reactive monoclonal antibodies, the Pteropus strain of ABLV demonstrated greater similarity to classical rabies than the other rabies-related lyssaviruses (Hooper et al. 1997). Commercially available rabies vaccines are cross-protective against ABLV infection in a mouse model (Hooper et al. 1997).

International Medicine

There are millions of people in the world today who need this kind of self-sacrificing care. They are refugees, displaced people, or victims of war, epidemics, starvation, disaster, neglect, and widespread infection (particularly tuberculosis, malaria, and AIDS). In regions like Africa, India, and Central America, volunteer doctors have many responsibilities. They deliver emergency medical care, perform surgery, administer vaccines, and help to construct new hospitals and clinics. They also train the local doctors about the latest medical care and educate the community about basic public hygiene. If this sounds appealing, it is easy to get involved as a volunteer physician. Organizations like Health Volunteers International, Doctors Without Borders, World Medical Missions, and many religious groups all sponsor short-term medical missions to third-world countries. International medicine gives every physician the opportunity to develop cultural sensitivity and to learn how to deliver...

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There appears to be a number of factors contributing to this phenomenon unrealistic expectations that the problem will soon be solved by vaccines and drugs a public view that the epidemic has leveled off or peaked and is declining in industrialized countries the belief that spread of AIDS among heterosexuals is not a serious problem in industrialized countries and fatigue about AIDS on the part of the media, politicians, and the public.

Katja Schmitz PhD and Ute Schepers PhD

RNA interference (RNAi) is an evolutionarily conserved phenomenon of double-stranded (ds)RNA-mediated mRNA degradation that leads to the posttranscriptional silencing of the corresponding gene. First reports on RNAi emerged in 1998, and since then, it has become one of the most fascinating fields of molecular biology. RNAi has provided important insights about the diversity of RNA molecules and their implication in many biological processes such as the regulation of developmental genes in eukary-otic organisms. Furthermore, RNAi has rapidly developed into a powerful instrument with a great potential for functional genomics and therapeutic applications by silencing normal and disease-related gene functions. To date, the use of RNAi for genetic-based therapies is widely studied, especially in viral infections, cancers, and inherited genetic disorders. Despite the many unanswered questions on how this technology can be efficiently applied to humans, the development of novel approaches,...

Divorce and children 151

Alternatively, diphtheria toxoid may be combined with tetanus toxoid alone (DT) and given to children, or combined with tetanus toxoid (Td) in an adult vaccine. The Td version only contains about 15 to 20 percent of the diphtheria toxoid found in the DTaP vaccine and is used for older children and adults. The vaccine, which was introduced more than 50 years ago, led to a dramatic reduction of the incidence of diphtheria throughout the world. Primary preventive programs aimed at immunizing all infants and children in the community have almost eliminated the disease. Yet while the reported incidence of diphtheria has been almost the same since the 1960s, it still occurs in isolated epidemics, primarily because some countries have taken a complacent attitude toward vaccination. The disease continues to represent a serious public health problem because it is possible for even fully immunized people to carry the C. diphtheriae bacteria in nose and throat, transmitting it to non-immunized...

Public Health Issues and Conclusion

The similarity between ABLV and RABV, the ability of vaccines to afford cross-protection in mice, and the neutralizing properties of human rabies immune sera led to the adoption of rabies pre- and post-exposure protocols for the prevention of ABLV infection in humans. According to Australian government health guidelines, it is recommended that individuals at risk of exposure, such as veterinary workers and wildlife handlers, should undergo a course of three intramuscular injections with inactivated human diploid cell-cultured virus vaccine (MacIntyre 2000). Vaccinated individuals exposed to either bat scratch, bite or on mucous membranes should be offered a booster vaccination. Exposed unvaccinated individuals should be offered human rabies immune sera in addition to five intramuscular injections of vaccine. The exception to these post-exposure protocols is when the offending bat has been demonstrated to be uninfected within 48 h of the exposure, by a recognized laboratory. These...

Scope of Agency Responsibilities and Activities

One widespread change in the scope of local public health agency activities is a reduction in the direct delivery of health care services, especially to Medicaid participants. This is consistent with a national effort to have governmental public health agencies return their attention to the more population-based public health services that had been weakened by the pressing need to provide safety-net services to uninsured individuals. Although some have been unable to do so, many state and local public health agencies now have contracts with managed care organizations and other private providers to serve those populations. A substantial transfer of service delivery from health departments to private providers has also occurred for childhood immunizations under federal and state programs for the purchase and distribution of vaccines (IOM, 2000a). Some researchers have found the partnership between managed care and local public health agencies to be positively associated with the overall...

Encephalomyelitis acute disseminated ADE

ADE appears more often in children and typically follows vaccination or infection. A variety of terminologies is used to describe it, including post infectious, parainfectious, or post-vaccinial ence-phalomyelitis. ADE predominantly affects the white matter of the brain under a microscope, an invasion of white blood cells around small veins can be seen. Where these cells accumulate, myelin is destroyed. The association of the disease with a prior infection or immunization suggests an immune system problem. Research of ADE patients found that their bodies mount an allergic response against their own brain constituents.

BS layers related to pathogenicity

Based on the data obtained in fundamental studies on S layers, a considerable potential in biotechnological and nonbiological applications is evident. Applications for S layers have been found in the production of isoporous ultrafiltration membranes, as supports for a defined covalent attachment of functional molecules (e.g. enzymes, antibodies, antigens, protein A, biotin, and avidin) as required for affinity and enzyme membranes, in the development of biosensors, or in solid-phase immunoassays. S-layer membranes have also been used as support for Langmuir lipid films or liposomes, mimicking the molecular architecture of gram-negative archaea and virus envelopes (see Fig. 23.1a). S-layer fragments or self-assembly products are well suited for a geometrically well-defined covalent attachment of haptens and immunogenic or immunostimulating substances. These haptenated S-layer structures act as strong immunopotentiators. Finally, cloning and characterization of genes encoding S-layer...

Putative Mechanisms of RV Neuroinvasiveness

Et al. 9 show that a G-deleted RV (4G) trans-complemented with RV G can infect neuronal cells but cannot spread to secondary neurons. While these experiments indicate the major role of the G protein in RV spread from the postsynaptic site to the presynaptic site, the RV P protein might be an important determinant of retrograde transport of the virus within axons. This hypothesis is supported by the demonstration that RV P interacts strongly with the dynein light chain LC8 19, 35 via a conserved (K R)XTQT motif 23 . Indeed, deletion of the LC8 binding region from RV P of the vaccine strain SAD-D29 led to a 30-fold decrease in the LD50 in 2-day-old suckling mice. However, the4LC8 RV still killed suckling mice at doses higher than 102 focus-forming units, suggesting that the LC8 binding site may not be the sole factor in the retrograde axoplasmic flow of RV 27 . Another unresolved issue concerning the potential RV P-mediated retrograde transport mechanism rests in the requirement for...

Endogenous TLR ligands

Furthermore, evidence for an involvement of an immune response towards heat shock proteins (HSPs) in the development of arteriosclerosis is accumulating (for a recent review, see 37 ). Heat shock proteins are among the most highly conserved protein families and are ubiquitously expressed in almost all mammalian tissues. In particular prokaryotic and human HSP60 share a high amino acid sequence homol-ogy (> 70 ). Immunologic cross-reaction between bacterial (e.g., Chlamydial) and human HSP60, which has been detected on the surface of stressed endothelial cells, might be involved in atherogenesis. Both, bacterial and human HSP60 signal through TLR4 and or TLR2 and lead to the activation of NF-KB-dependent proinflammatory gene targets 38-41 . Chlamydial HSP60 was shown to lead to human SMCs proliferation in a TLR4-dependent manner 41 . Nasal vaccination with mycobacterial HSP65 has been demonstrated to reduce inflammation and decrease atherosclerosis in aortic arches in LDL...

Eyewear protective 177

Expression system In genetic engineering, the cells into which a gene has been inserted to manufacture desired proteins. Chinese hamster ovary (CHo) cells and baculovirus insect cells are two expression systems that are used to make recombinant HIV vaccines. In HIV vaccine production, the system is composed of cells into which an HIV gene has been inserted to produce desired HIV.

Is Disease Prevention Possible

The safest and most rational form of primary prevention would be modification of environmental determinants of disease. Leading candidates in type 1 diabetes are viruses and infant nutrition. The congenital rubella syndrome is sometimes cited as evidence that a virus can cause type 1 diabetes, and that type 1 diabetes can be prevented by routine rubella vaccination. It is, however, far from certain that children with this syndrome have typical type 1 diabetes, and some clearly have an insulin-resistant form of the disease. Associations between enteroviral exposure in utero and subsequent development of diabetes in the child6,7 raise the possibility that women might at some future date be vaccinated against a range of viruses, but the evidence base for such an intervention is far from established. The alternative environmental explanation, that exposure to cows' milk at an early stage of development might be diabetogenic, remains controversial8. The hypothesis is, however, susceptible...

Information Systems and Communications Tools

The recommendations of the 1995 report have also led CDC to develop NEDSS (CDC, 2000b). Although the system is now in the early stages of development, one of its objectives is to electronically integrate a variety of surveillance activities, including the National Electronic Telecommunications System for Surveillance and the reporting systems for HIV AIDS, tuberculosis, vaccine-preventable diseases, and infectious diseases. It is also intended to facilitate more accurate and timely disease reporting to CDC and state and local public health departments. NEDSS will incorporate data standards, an Internet-based communication infrastructure that is designed according to industry and public policy standards on data access and sharing, confidentiality protection, and burden reduction (CDC, 2000b).

GALT gutassociated lymphoid tissue

Gamma globulin A type of protein found in the blood. It is made up of antibodies. When gamma globulins are extracted from the blood of many people and combined, they can be used to prevent or treat infections. They are used in what are sometimes called vaccines for hepatitis A and chicken pox. Gamma globulins are synthesized by lymphocytes and plasma cells in response to an antigenic challenge. The ability to resist infection is related to concentration of such proteins.

Conclusions Future investigations and therapeutic potential

Innate immunity represents an attractive source of therapeutic targets because it is linked directly to development of atherosclerosis, and also because of its strategic position in controlling inflammation, autoimmunity, and antibody responses. Lig-ands for specific TLRs are already being developed and evaluated in clinical trials as vaccines or adjuvants 93, 94 . Innate immune cells, particularly DCs, are being evaluated for possible roles in delivering antigen and inducing antitumor immunity 95 and in controlling autoimmunity 96 . Therapies aimed at tipping the Th1 Th2 balance toward a Th2 response may be a fruitful area of investigation among these are molecules that target specific aspects of TLR signaling 93 . NK cells and NK T cells may be useful in treating cancer 97 , and since both have been recently linked to atherosclerosis 98, 99 , the possibility arises that cellular therapy utilizing these lineages might also prove useful in atherosclerosis. Although still in early...

Mucins In Diagnosis And Therapy

The immune system has the potential to recognize such TAA structures as foreign and to mount specific immune responses against them, so as to reject tumor cells. This provides the basis for the development of active specific immunotherapeutic agents (tumor vaccines). The first mucin cDNA to be cloned, MUC1, is highly overexpressed and differentially glycosylated by pancreatic adenocarcinomas and is a cell surface-associated mucin with a structure that is remarkably similar to some of the selectins and selectin ligands. There have been studies that evaluated the effect of immunizations with MUC1 on immunity to tumors in animal models. Vaccine strategies against MUC1 include DNA, peptide, glycopeptide, fusion proteins, and recombinant vaccines delivered by adenovirus, vaccinia virus, and other viral vectors, administered directly or in vivo to manipulated cells.

Genital secretions 197

Genetic variability The variability in genetic sequences of a life form. In human beings and other forms of higher life there is no more than 5 percent variation in genetic sequences from person to person, cow to cow, or even Escherichia coli to Escherichia coli. However, viruses have much more variability. Viruses have up to 35 percent difference between individual viruses. Retroviruses in particular have nearly 35 percent mutability. This mutability makes creating drugs or vaccines that can work against all of the possible variations of a particular virus such as HIV difficult. The efficacy of vaccines depends on their capacity to cover an increasingly broad spectrum of variants, as HIV changes from person to person, continent to continent. Biopharming represents another point on the continuum. In general, biopharming appears to be a creature of giant corporations, not family farms. Boosters of biopharming insist that their products will be cheaper than current drugs. Examples...

Go both ways See bisexual

Gp120 A glycoprotein on HIV's envelope that binds to the CD4+ molecules and chemokine receptors on cells' outside membrane. Free gp120 in the body may be toxic to cells, by causing CD4 cell depletion in the immune system through apopto-sis and neurological damage leading to hiv encephalopathy. It is one of the areas of focus in vaccine development because it is the outer part of the virus that encounters antibodies.

Habits vs Mental Problems

Child in every 20 who gets meningitis dies, and up to 35 percent of those who live develop permanent brain damage. However, widespread use of a vaccine licensed for infants in 1990 has dramatically reduced the incidence of a deadly disease that only 10 years ago killed 800 infants each year in the United States. According to the CDC, the incidence of invasive Hib infection has dropped by almost 98 percent among infants and children since the introduction of the vaccine. Although the disease is not yet completely eradicated, the vaccine has been stunningly effective.

Diverse Uses for Mouse Models of Cancer

Vaccination has been an effective defense against both bacterial and viral diseases. Research to develop vaccine-based cancer immunotherapy targeting tumor-associated antigens (TAAs), although still at an early stage, is proceeding with the assistance of transgenic mouse models. A major concern in the development of such therapeutics is that because TAAs are self-antigens, the benefit of an antitumor effect must not be outweighed by a pathological autoimmunity particularly with the addition of costimulatory molecules to increase vaccine potency. Carcinoembryonic antigen (CEA) overexpression, for example, has been associated with a variety of carcinomas, but does exhibit a limited normal tissue expression and is thus considered both a TAA and self-antigen. In a series of studies, a mouse model engineered to correctly express the human CEA has proved useful in evaluating autoimmune reactions. The model permitted a comprehensive evaluation of vaccine effects by biochemical,...

Applications And Commercial Relevance

The recombinant DNA technology, including screens based on the detection of DNA by hybridization to a specific probe and the analysis of DNA sequence, is now basic to all fields of biology, biochemistry, and medical research as well as the biotech industry. Tests dependent on DNA are used to identify contaminants in food, parents of children, persons at the scene of a crime, and the putative position of a specimen in a phylogenetic tree. Mutations in specific genes may be made, their nature confirmed, and their effects monitored. Gene products may be amplified for study and use as experimental or medical reagents. Hormones, cytokines, blood-clotting factors, and vaccines are amongst the medically relevant proteins that have been produced in microorganisms, obviating the need to isolate them from animal tissues.

Comparative genomics

The resources required for a microbial whole-genome sequencing project is not insignificant, with a cost of approximately 1 million and requiring 1 or 2 years to complete. However, high-throughput sequencing of microbial DNA is the most cost-effective method to obtain genomic information a typical microbial genome would give several thousand gene sequences at a cost of several hundred dollars per gene (significantly less than the per gene cost of the pregenomic era). This cost is reduced even further by sequencing at a lower average redundancy (3-6 X coverage), providing a catalog of the majority of the genes in an organism of interest. These data are sufficient for the purpose of rapidly acquiring a proprietary database of genomic data, often from multiple organisms, and performing functional genomics work with the ultimate goal of producing vaccines or antibiotics. However, the goal of the complete genome project, published in a peer-reviewed journal, is to sequence every base pair...

Other functional studies

Numerous functional studies in addition to those mentioned previously are being performed for sequenced bacteria. This list is not inclusive, and it should again be mentioned that the most well-coordinated functional analysis programs currently being performed are those for B. subtilis and S. cerevisiae. Methods currently being used include (i) reporter fusion analyses, constructed for entire genomes, to provide gene expression data using whole cells (ii) protein-protein interactions to determine what proteins interact with each other in a cell are providing important information to be used in conjunction with gene function studies (iii) protein overexpression, using a high-throughput, brute-force protein overexpression methodology involving designing primers to the 5' and 3' ends of sequenced genes, cloning into T7 polymerase-driven vectors with affinity tags, and expressing and purifying the gene products using E. coli, with purified protein being used for numerous applications...

HIV Network for Prevention Trials HIVNET

A group funded by The National Institute of Allergy and Infectious Diseases (NIAID) that conducts domestic and international multicenter trials to evaluate promising interventions to prevent the transmission of HIV. Interventions studied include HIV vaccines, topical microbicides, sexually transmitted disease treatment, prophylaxis to prevent vertical transmission, and behavioral risk reduction strategies. in western Africa eating of monkey meat is part of the culture. Many green monkeys are killed for this purpose. in addition their abandoned or orphaned young are often taken home as pets in this region. So it is not difficult to see that a pet could have bitten a person or that while cleaning the monkey for eating someone got blood on a cut and was infected in that manner. it is assumed that HIV-1 was spread in the same manner in west central Africa. Scientists believe that given the rate of change of HIV, it was probably introduced into the human population after the 1930s. It is...

A 25year Perspective

In the Democratic Republic of the Congo (DRC, formerly Zaire), the decrease in smallpox vaccination coverage, poverty, and civil unrest causing humans to penetrate deep into the tropical rain forest in search of food may have resulted in breeches in the species barrier between humans and animals, causing an extended and continuing outbreak of human mon-keypox. During the 1970s and 1980s, when this zoonotic disease was the subject of extensive studies, it was shown that the monkeypox virus infected humans, but that person-to-person transmission beyond three generations was rare. The outbreak of

Results And Discussion

Our data show that while there are obvious similarities in the localization of SARS-CoV structural proteins and those of other coronaviruses, there are apparent differences. Ultimately, it will be important to compare our data with staining patterns seen in SARS-CoV infected cells to get a complete picture of where these structural proteins localize in the context of the other viral proteins. Understanding viral protein trafficking and identifying which protein(s) directs the site of virus assembly will help us develop antiviral drug platforms and possible vaccines to combat this important pathogen.

Constraints on innovation

There has been a de facto European Union moratorium on the approval of GMO products since October 1998. Eighteen products have already been approved under the general EU Directive (90 220 CEE) whilst 14 are pending approval. Five Member States have temporarily banned already approved GM products, which is permitted under the Directive. Two new EU labelling regulations have been drafted but have not been implemented because of a lack of testing methodologies, certifying labels and inspection procedures. The ultimate intention is to ensure that products can be labelled GM free to enable consumers to make an informed choice. It has been argued that products labelled as containing products derived from GM will convey negative messages to consumers. This is likely to be so in the absence of benefits that are clearly seen by consumers. This will occur if plants are used as factories for the production of vaccines and pharmaceutical products. However, it is unclear at present where these...

Misplaced Optimism

In this same 25-year period the eradication of smallpox was achieved. This unparalleled public health accomplishment resulted in immeasurable savings in human suffering, death, and money, and stimulated other eradication initiatives. However, recent concerns about the possible deliberate use of variola virus as a biological weapon prompted some countries to consider introduction of population-wide preemptive vaccination, but after close deliberation WHO recommendations of October 2001 were accepted by most countries. The WHO is currently leading international initiatives to eradicate poliomylitis and dracunculiasis and to eliminate African trypanoso-miasis, Chagas disease, leprosy, lymphatic filariasis, onchocerciasis, and blinding trauchoma. Since the global polio eradication initiative was launched in 1988, three regions have been certified as free of the disease the Americas in 1994, the Western Pacific in 2000, and Europe in 2002. Reported cases of polio have dropped from an...

Weaknesses Facilitating Emergence And Re Emergence

The weakening of the public health infrastructure for infectious disease control is evidenced by failures such as in mosquito control in Latin America and Asia with the re-emergence of dengue now causing major epidemics in the vaccination programs in eastern Europe during the 1990s, which contributed to the re-emergence of epidemic diphtheria and polio and in yellow fever vaccination, facilitating yellow fever outbreaks in Latin America and sub-Saharan Africa, including a large urban outbreak that occurred in Cote d'lvoire in 2001. It is also clearly demonstrated by the high levels of hepatitis B and the nosocomial transmission of other pathogens such as HIV in the former USSR and Romania, and the nosocomial amplification of outbreaks of Ebola in Zaire, where syringes and failed barrier nursing drove outbreaks into major epidemics.

Vaccinating for Animal Health

In the fight against disease agents in domestic animals, another intriguing GM approach, DNA vaccination, was prompted by an article that appeared in a 1990 issue of the journal Science. Researchers demonstrated that pieces of viral DNA, when engineered into a suitable expression vector and injected into mice, were incorporated and successfully activated in the animals' muscle tissue, thereby potentially inducing a protective immunity against the virus. Ten years later, another research team showed that such immunity potential could be realized. In this case, they inoculated rainbow trout with a plasmid DNA concoction containing an antibody sequence specific for a rhab-dovirus that causes fish hemorrhagic septicemia (a debilitating blood infection). The fish responded by producing antibodies that afforded protective immunity against the virus. Such recombinant DNA vaccines include specific transgenes that, after injection, activate within the recipient's body to produce and distribute...

Intraocular implant 263

International unit (IU) The internationally accepted quantity of a substance. This type of measure is used for the fat-soluble vitamins (such as vitamins A, D, and E) and certain hormones, enzymes, and vaccines. International units are officially defined by the International Conference for unification of Formulae.

Parenteral controlled release systems

Several controlled release parenteral delivery systems have been investigated for the delivery of therapeutic peptides and proteins. These include microspheres, implants, liposomal delivery systems, nanoparticles, vaccines, and pulsatile drug delivery systems. Besides these approaches, cellular carriers such as erythrocyte vesicles can also be used for controlled release of proteins. The binding of human insulin to erythrocyte membrane by encapsulation or adsorption has been described.80 Also, antibodies are under investigation to provide target site specificity, especially for anticancer drugs to minimize their side effects.

Role Of Pili In Disease Processes

During the infection process, adhesive pili are often situated at the interface between host and pathogen where they can potentially mediate cross-talk between the two organisms. A few examples of pilus attachment inducing signal-transduction pathways in host eukaryotic cells have been reported. The binding of the type 4A pili of Neisseria to host receptors (probably CD46) on target epithelial cells has been shown to stimulate the release of intracellular Ca2+ stores, a signal known to control a multitude of eukaryotic cellular responses. Similarly, the attachment of P pili to Gala (1-4)Gal-containing host receptors on target uroepithelial cells can trigger the intracellular release of ceramides, important second-messenger molecules that are capable of activating a variety of protein kinases and phosphatases involved in signal trans-duction processes. The signals induced in uroepithe-lial cells upon the binding of P-piliated bacteria eventually result in the secretion of several...

Casecrossover Designs

Example - case-crossover design - MMR vaccine and aseptic meningitis Park, Ki and Yi (2004) describe a study looking at the link between the mumps-measles-rubella vaccine and the occurrence of aseptic meningitis. From 420 confirmed cases, they eventually found 39 with accurate vaccination records. They chose the window period to be w 42 days and the control period the year preceding the event, excluding the window period, i.e. 365 42 323 days. Among the 39, they found 11 vaccinated during the window (hazard) period and 28 during the control. Since the control period is the same for each subject, the odds ratio for the risk of meningitis due to MMR is simply the ratio of the two incidences (11 42) (28 323) 3.0 (95 CI 1.5 to 6.1). Maclure and Mittleman (2000) discuss the use of case-crossover studies and state that the design applies best if the exposure is intermittent, the effect on risk is immediate and transient and the outcome is abrupt. Farrington (2004) points out that the...

Treatment And Prevention Of Systemic Fungal Infections

There are ongoing efforts to develop vaccines against coccidioidomycosis, histoplasmosis, and cryptococcosis but none is currently available. At this time, the two main strategies for the prevention of systemic infection in patients at risk for infection include avoidance of infection and the use of prophylactic antifungal drugs. For many systemic fungal infections, prevention is difficult because the fungal pathogen is highly prevalent in the environment. For example, C. neoformans is found in high concentration in pigeon excreta in urban areas such as New York City, where many patients with advanced HIV infection live. Similarly, H. capsulatum and C. immitis are prevalent in soils of specific geographic areas of the world and avoiding exposure may be difficult for residents in those regions. Nevertheless, it is prudent for individuals with immunological disorders to avoid sites likely to contain high concentrations of aerosolized fungal pathogens such as construction sites,...

March of Dimes Birth Defects Foundation A

The March of Dimes was founded in January 1938, when President Franklin D. Roosevelt, himself a polio victim and alarmed by decades of worsening polio epidemics, established the National Foundation for Infantile Paralysis. At the time, comedian Eddie Cantor coined the phrase March of Dimes (playing on the popular newsreel feature The March of Time), appealing to radio listeners all over the country to send their dimes directly to the White House. The campaign was extremely successful, and over the next 17 years, the National Foundation focused on funding research to develop a vaccine against polio. In 1948, with funding provided by the March of Dimes, Dr. Jonas Salk was able to grow the three known types of polio virus in his lab and eventually to develop an experimental killed-virus vaccine. In the summer of 1952 Dr. Salk tested the vaccine on children who had already recovered from polio. Following vaccination, the level of polio antibodies in their blood increased. The next step...

National Cancer Institute NCI One of the

National Institute of Allergy and Infectious Diseases (NIAID) NIAID is the U.S. government agency that provides major support for scientists conducting research aimed at developing better ways to diagnose, treat, and prevent infectious, immunologic, and allergic diseases that afflict people worldwide. It is a division of the national institutes of health. It is responsible for the national basic research program in AIDS, which is managed through the division of aids. The institute supports basic research, epidemiology, vaccine development, drug discovery and development, and treatment studies. It administers the adult aids clinical trials group (AACTG), the pediatric aids clinical

Research outside of containment

Any research with GMOs that is to be conducted in facilities that are not specified in the NIH guidelines is considered a planned introduction into the environment. Under current policies, such research, regardless of the funding source of the researcher, is subject to regulations of either the USDA or EPA. Neither agency has a codifications similar to that of NIH for contained research. Instead, each introduction is treated as a distinct case and application must be made by the investigator to the appropriate federal agency for permission to conduct the research. This includes all research with genetically modified microorganisms, plants, animals, and vaccines. The current status of each agency and of approval processes can be obtained most readily by viewing their home pages. Each of the agencies has recently published policy statements or has issued Final Rules describing how regulations they enforce are applicable to research with GMOs.

Recovery of IHNVfrom cDNAs

The ability to generate infectious virus derived from cDNA is a very powerful approach, since the viral genome can be manipulated to generate attenuated vaccine strains and also makes the introduction of genetic tags feasible, thus discriminating between field and the vaccine strains. Moreover, an extra gene can be stably introduced into the viral genome, and thus negative-strand RNA viruses such as IHNV could be used as a gene vector (Conzelmann 1998 Pekosz et al. 1999). To evaluate the feasibility of generating a live attenuated viral vaccine strain to prevent IHNV infection in the field, a reverse genetic system for IHNV allowing recovery of genetically tagged infectious virus through cDNA transfection into fish cells has been developed.

Viral subversion of innate immunity through TLRs

The haemaglutinin (HA) protein of wild-type, but not vaccine strains of measles virus activates murine and human cells via TLR2, leading to induction of proin-flammatory cytokines such as IL-6 in human monocytic cells, and upregulation of surface expression of CD150, the receptor for measles virus 58 . Hence, activation of TLR2-dependent signalling by wild-type measles virus is likely to contribute to both immune activation and viral spread and pathogenicity. Thus, the loss of TLR2-activating capability may be considered as an attenuation marker.

Targeted Modifications of the IHNV Genome Exchange of VHSV and IHNV Proteins

As the final goal of establishing a reverse genetics system for IHNV is the development of attenuated live vaccine administrable through bath immersion, it is important to demonstrate that the IHNV genome can be manipulated. The first approach was to see whether the gene encoding the IHNV G could be replaced by other heterologous G genes. Thus, the IHNV genome was engineered such that unique restriction enzyme sites (Spel and Smal) were added at the initiation and the stop codon of the G open reading frame. To replace the IHNV G gene, G genes from the VHSV and the spring viremia of carp

Novel antiangiogenic strategies

Table 3 shows the multitude of other agents being developed to target VEGF and its receptors. These agents are in all phases of clinical trials as single agents or in combination with chemotherapy. In addition to the VEGF VEGFR axis, other targets are also being explored, including angiopoietin Tie receptors, EGF EGFR, ephrins Eph receptors, PlGF, bFGF, TNF, and others. Many of these strategies have undertaken antibodies as drugs with the advantage of specificity and stability of these large molecules. However, small-molecule drugs and peptides are also being widely explored. Finally, novel experimental approaches using gene therapy, vaccines, and antiangiogenic radioligands are being evaluated in the preclinical setting for potential use in future clinical trials (13).

Proangiogenic factors 21 VEGF

Vaccine Vaccine An alternative to gene therapy is the use of catalytic oligonucleotides to inhibit VEGF receptors. A ribozyme targeting VEGFR1, upregulated in mitogenic endothelial cells, has been reported to have significant antitumor activity in animal models (27). Similar to ribo-zymes, VEGFR2 DNAzymes have demonstrated marked antitumor efficacy in vivo with a 75 reduction in tumor size compared to controls the potential advantages of DNAzymes compared to RNAzymes include greater resistance to nucleases and the ability to digest mRNA at the start site, a region with little secondary structure (28). (In Section 4, antitumor vaccines directed toward VEGFR2 and FGFR2 are discussed.)

Materials And Methods

Vaccine and Challenge Virus Three different inactivated vaccines were used in the experiments one based on a commercial, European type attenuated vaccine virus, one based on Marc-145 grown Lelystad virus (5th passage) and one based on porcine alveolar macrophage grown Lelystad virus (13th passage). Viruses were concentrated and semipurified by ultracentrifugation at 100,000 x g for 3 hours through a 30 sucrose cushion in an SW41 Ti rotor (Beckman Coulter Inc.). Virus was then inactivated with beta-propiolactone and formulated in a water oil emulsion so that each 2 ml dose of vaccine contained an equivalent of 1080 TCID50. A total of 26 pigs were obtained from PRRSV naive sows at the age of 4 weeks. The pigs were randomly divided into 4 groups and housed in isolation units with HEPA filtered air. The designation of the groups and the experimental design is shown in Table 1. At 6 and 10 weeks of age, the pigs were vaccinated intramuscularly with the designated vaccine. Four weeks...

Post Crisis Efforts and Persistent Problems

China's rigid science and technology system is partly to blame for having not responded to the SARS crisis quickly and effectively that system has not changed in the post-crisis environment. The difference is that it has just gone to the other extreme each institution, regardless of its capability and expertise, wants to conduct SARS-related research. China's scientific leadership has ever since made moves to support the SARS research, especially on the search of vaccines that would permanently dismantle the disease. But there is still no coordination of research efforts at different jurisdictions so that there could be enormous waste of human and financial resources. Second, because of the visibility of the SARS research and subsequent institutional support and engagement, there has been a new great leap forward. Researchers have announced one achievement after another through the news media with the focus on the advancement in the SARS vaccines. Although many of the announcements...

Animal Models For Sars

In 2002-2003, severe acute respiratory syndrome (SARS) was a newly identified illness that emerged in Southern China, spread to involve more than 30 countries, and affected more than 8000 people and caused nearly 800 deaths worldwide. Although the etiologic agent was rapidly identified to be a previously unknown coronavirus (named SARS coronavirus or SARS-CoV) and the outbreak was controlled by public health measures, no specific options were available for prevention and control of human disease. Over the past two years, a number of strategies for vaccines and immunoprophylaxis have been investigated. Animal models are essential for preclinical evaluation of the efficacy of candidate vaccines and antivirals, and they are also needed in order to understand the pathogenesis of SARS. A number of investigators around the world have evaluated several different animal species as models for SARS this effort is important for two reasons. First, because the source of SARS-CoV in the wild is...

PMN polymorphonuclear cell See neutrophil PMPA See tenofovir

Pneumococcal vaccine A vaccine to immunize against the most common cause of bacterial pneumonia in HIV-negative people, the bacterium Streptococcus pneumoniae or pneumococcus. Pneu-mococcus is also a common cause of pneumonia in people with HIV infection. Pneumococcal vaccine is recommended for anyone who is especially prone to frequent or severe infection by pneumo-coccus. It is best for those with HIV to take this vaccine relatively early in the course of the disease when the immune system is strong. pneumococcus An oval-shaped, encapsulated, non-sporeforming, gram-positive bacterium occurring usually in pairs having lancet-shaped ends. There are more than 80 serological types of pneu-mococci. In addition to causing pneumonia, pneu-mococci are found to cause infections such as bronchitis, conjunctivitis, keratitis, mastoiditis, meningitis, otitis media, and bloodstream infections. A pneumococcal vaccine is available. Pneumococcal infections are effectively treated with penicillin or...

Poison sumac Toxicodendron vernix [L Kuntzel [Rhus vernix L This poisonous tree a relative of poison ivy and poison oak

Poliomyelitis (polio) A contagious viral disease that in its severe form can cause permanent paralysis and sometimes death. This extremely dangerous disease causes mild disabilities in about half of all patients the rest may suffer permanent paralysis. However, due to modern vaccination practices, the Americas were declared polio-free in 1994, and the disease has been almost eliminated in Europe (there was an outbreak in the Netherlands in 1995). The global network of labs that track the disease reported no new cases of Type 2 polio in 2000. The last recorded cases were in India in 1999.

Topical delivery of therapeutic peptides and proteins

Much of the literature for peptide drugs currently focuses on transdermal delivery, that is, percutaneous absorption for systemic effects. However, topical delivery of peptide and protein drugs is also of great importance one example is the use of growth factor for wound healing. Biotechnology products in development for skin disorders include the recombinant proteins onercept and interleukin (IL) 18bp, the fusion protein denileukin diftitox, and the monoclonal antibodies eculizumab, adalimumab, and antiangiogen-esis monoclonal antibody.137 Proteins can also be used as antigens for topical delivery for vaccination, and such use is discussed in Chapter 10.

Concluding Observations

Academia has made major contributions to prolonging life and increasing the quality of life through research. Basic research has provided the knowledge necessary to develop precious vaccines that protect against debilitating and deadly diseases, whereas research on the determinants of health has demonstrated the importance of social and behavioral factors to health. However, comparatively few resources have been devoted to supporting prevention research, community-based research, or the translation of research findings into practice. Such resources must be found and allocated if academia is to continue to have a major impact on the health of communities. With the collaboration and partnership of academia, scholarly service has the potential to make great strides in engaging the community in improving its own health. However, without a restructuring of the reward system within universities and colleges, this most promising approach to change encounters barriers that are difficult to...

Public assistance See public aid

Public Health Service Act Legislation signed by the president July 1, 1944, and administered by the FOOD AND DRUG administration (FDA). The act gives the FDA authority to ensure safety, purity, and potency of vaccines, blood, serum, and other biological products. It also empowers the FDA to ensure the safety of pasteurized milk and shellfish, as well as the sanitation of food services and sanitary facilities for travelers on buses, trains, and planes. See food and drug act of 1906.

Role of E5 Proteins in the Virus Life Cycle and Carcinogenesis

E5 protein may play a role in carcinogenesis (Bible et al., 2000 Bravo et al., 2005 Schiffman et al., 2005). The nature of this role is not known, but it may reflect the ability of the HPV E5 protein to inhibit immune function, apoptosis, or gap-junctional communication. It is possible that vaccination could elicit E5-specific cytolytic T-lymphocyte-mediated killing of precancerous cells or even carcinoma cells that express the E5 protein (Chen et al., 2004, Liu et al., 2000).

Recombinant live vectors See live recombinant

VECTOR VACCINES. recombinant subunit vaccines Vaccines that use viral proteins produced by using recombinant DNA technology. In this case, recombinant DNA technology involves transplanting the genes for certain HIV proteins into bacteria or other microorganisms or into mammalian cells. The host cells then churn out large quantities of the recombinant HIV protein. This method of production is a safer and more cost-effective way to obtain large quantities of HIV protein than the alternative which requires growing large amounts of infectious HIV particles. Recombinant GP160 proteins and P24 proteins have been tested in early clinical trials. Their apparent drawback resides in a component of the recombinant product that was subtly different from that of the natural HIV proteins. As a result, the antibodies elicited by the recombinant proteins did not effectively neutralize strains of HIV that are commonly transmitted.

Reproductive decisionmaking 421

To HAART from earlier, less effective regimens. Smaller trials continued that included Remune plus haart. In the summer of 2001, Pfizer, which was codeveloping Remune with Immune Response Corporation, dropped its sponsorship. This left Remune without any substantial funding for further research. The only side effect noted was irritation at the injection site. Other names are HIV-1 immunogen. It is sometimes referred to as the Salk vaccine.

Respiratory tract infections

Synagis and RespiGam are not vaccinations, but they can help protect high-risk children under age two from the most serious complications. Injections of either of these drugs are typically given once a month during the RSV season (November through May). One injection protects the baby for one month, so an injection is needed every month during the RSV season to be fully protected. No vaccine for RSV currently exists, although some researchers are testing various versions of a live attenuated RSV vaccine. Because RSV spreads in fluids from the nose and throat of an infected person, washing hands and avoiding touching nose or eyes after contact with someone with RSV can help prevent the spread of the disease. Since a baby is most vulnerable during the first three months of life (especially those born during the winter), it is possible to take some steps to protect the baby by

Sexually transmitted disease 447

Researchers have been concerned about the possibility that STDs might accelerate the progression of HIV disease. This concern is based on observations that activation of the body's immune system, through either infections or administration of vaccines, may temporarily increase viral load. Although the clinical importance of such viral load increases is not definitively known, studies of HIVpositive persons with tuberculosis an infection that may cause increases in HIV viral load have demonstrated more rapid HIV disease progression. Researchers have questioned whether similar effects could be caused by STDs. An increase in the amount of genital secretions has been noted with several different STDs, but it is not clear whether this increase in HIV replication is confined to the genital compartment or is more widespread in the body. Because some STDs, such as syphilis, cause widespread immune stimulation, an increase in plasma viral load would be predicted.

Identification Of S Protein Rbd As A Major Target Of Neutralizing Antibodies

We further observed that the RBD of S protein was a major target of neutralizing antibodies in mice and rabbits immunized with an inactivated SARS-CoV vaccine. All mice and rabbits developed high titers of antibodies against the S protein and its RBD after three immunizations.11 The mean end-point titers of mouse and rabbit antisera to the RBD were 1 51,200 and 1 25,600, respectively. Both mouse and rabbit antisera could efficiently block binding of RBD-Fc to ACE2. By using pseudovirus bearing the SARS-CoV S protein, we demonstrated that both mouse and rabbit antisera significantly inhibited S protein-mediated virus entry with mean 50 inhibitory titers of 1 7,393 and 1 2,060, respectively. To further elucidate neutralization determinants of the SARS-CoV, the RBD-specific antibodies were isolated by immunoaffinity chromatography from the rabbit antisera. Similarly, the reactivity of anti-RBD antibodies in the rabbit antisera could be efficiently depleted by RBD-Fc affinity column, as...

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