Vaccines for the 21st Century A Tool for Decisionmaking (2000) / Chapter Skim
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Progress in Vaccine Development
Progress in Vaccine Development
Pages 17-38
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From page 17... ...
conducted by the Committee on Issues and Priorities for New Vaccine Development at the request of the National Institute of A1lergy and Infectious Diseases (PLAID) of the National Institutes of Health (NIH)
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From page 18... ...
Initially, acellular pertussis vaccines were recommended only for the fourth and fifth doses of the childhood immunization schedule, but acellular pertussis vaccines are now recommended for all doses in the immunization schedule beginning at 2 months of age. Their diminished local reactivity and systemic manifestations have rendered them highly acceptable to both health care providers and parents.
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From page 19... ...
Influenza virus A and B Var~cella-zoster virus Group B streptococcus Parainfluenza viruses Cytome g al o virus Rotav~uses Neisserza gonorrhoeae Hepatitis A virus Coccidioides immitis Herpes simplex 1 and 2 Bordetella pertussis Cold-adapted live, attenuated virus vaccine in phase III trials; baculovirus-expressed recombinant HA subunit In phase III Dials. Live attenuated virus licensed arid in use.
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From page 20... ...
Influenza virus vaccines consisting of both attenuated live virus variants and a number of subunit preparations are also under continuing research and development. In contrast, the likelihood of successful licensure of parainfluenza virus vaccines, cytomegalovirus (CMV)
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From page 21... ...
A discussion of the principles and problems surrounding immunization of pregnant women is necessary to understanding this barrier to vaccine development, which has not been resolved since the 1985 report. Preventing infections in neonates and young infants by vaccinating pregnant women is a concept that is more than a century old.
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From page 22... ...
Scientific evidence pales when concern over the liability of vaccine manufacturers arises, and vaccine manufacturers appeal to the government for indemnification before they pursue studies of existing vaccines or the development of additional reagents appropriate for immunizing pregnant women. The committee reviewed immunization of pregnant women as a vaccination strategy in some detail, believing it to be scientifically valid for use in the United States for preventing several infectious diseases in young infants.
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From page 23... ...
Before reviewing some of the major biomedical advances that are allowing vaccine development to proceed in ways not previously imagined, it will be useful to take a look at one of the vaccine successes known to all- the development of polio vaccines and the near eradication of a dreaded disease. Disease Burden Poliomyelitis was a relatively insignificant disease in the United States before 1900, when epidemics of increasing severity began to appear in different parts of the country.
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From page 24... ...
Polio Vaccine Development Efforts to develop immunoprophylaxis against polioviruses began immediately after the isolation of the virus. Both killed and live virus candidate vaccines were developed as early as 1910, although at that time knowledge of the existence of three distinct poliovirus types was not available, and the fact that paralytic cases of polio represented only a tiny fraction of the total number of infections was not appreciated (Harrington, 1932, The National Foundation, 1961, 1962~.
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From page 25... ...
Occasional cases of disease were reported in fully vaccinated subjects in the early phases of the vaccination program, so continued efforts in vaccine development led to improvements in its biologic activity and the introduction of enhanced-potency IPV (eIPV)
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From page 26... ...
This policy assures the protection of the population against natural infection of those immunized against the rare but real possibility of adverse effects of vaccination. As the polio success story demonstrates, active vaccine development efforts in the face of changing epidemiology, scientific advances in basic virology, licensure of more than one polio vaccine, improvements in existing polio vaccines, worldwide efforts at eradication, and re-evaluation of domestic vaccination policies have all been necessary to give the U.S.
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From page 27... ...
Most virus-specific CTLs are CD4-, CD8+ and recognize viralus peptides in association with MHC class I expressed on infected target cells. Since CTLs have been shown to be important effector cells for eliminating virus-infected cells, it will be of considerable importance to continue to determine the significance of antigen-specific CTL responses in mucosa-associated tissue, where most virus infections actually occur (see below)
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From page 28... ...
The use of vaccines that induce protective mucosal immunity thus becomes attractive when one considers that most infectious agents come into contact with the host at mucosal surfaces. Induction of mucosal immune responses may not only protect the host from morbidity and mortality due to infection but may possibly prevent infection altogether.
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From page 29... ...
Studies to elucidate the common mucosal immune system pathway showed that immunization of one mucosal inductive site could induce mucosal immune responses in all mucosal effecter tissues. The common mucosal immune system provides a unique opportunity to develop mucosal vaccines that can be delivered orally or intranasally but that subsequently result in mucosal immunity at sites where immune protection is most desirable.
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From page 30... ...
Antigen-specific IgA presumably forms immune complexes with the colonizing pathogen and thereby inhibits the interaction of the pathogen with host epithelial cells, a protective mechanism known as immune exclusion (Mestecky and McGhee, 1987~. In fact, passive transfer of monoclonal IgA antibodies by a backpack hybridoma method provided protection against mucosal challenge with virulent organisms but was generally unable to prevent infection when the organisms were introduced parenterally, suggesting that mechanisms for protection at a mucosal surface do not correlate with protection from systemic challenge (Michetti et al., 1992~.
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The microspheres produced in this way are spherical. Those ranging from 1 to 10 g are most effectively taken up by antigen-presenting cells as well as ~ cells in mucosal inductive sites (Eldridge et al., 1990~.
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From page 32... ...
This vaccine induces both mucosal and systemic immune responses and offers protection from infection. Polio-virus-specific MHC class II-restricted CD4+ T cells in peripheral blood mononuclear cells from orally vaccinated individuals have also been detected.
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From page 33... ...
It has been known for a long time that the use of live, attenuated vaccines results in more appropriate and protective immune responses than does the use of inactivated vaccines. Expression of antigens in the host results in the correct protein conformation and glycosylation patterns.
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However, in nature, most foreign antigens are first confronted by the mucosa. Thus, gene administration to the mucosal surfaces would mimic exposure to most pathogens and may more efficiently induce a protective immune response.
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From page 35... ...
Examples of these diseases include diabetes, rheumatoid arthritis, multiple sclerosis, thyroiditis, myocarditis, and systemic lupus erythematosus. Within the last 15 years, the subfield of autoimmunotherapy within immunology has made impressive strides, along with the detailed knowledge of the initiation and propagation of autoimmune diseases.
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From page 36... ...
Fourth, treatments directed against an important receptor or its mediator can have a curative effect in some cases. Finally, viral vectors carrying genes coding for specific antigen products, and/or ameliorating agents such as cytokines and chemokines have been shown to be potent response modifiers.
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From page 37... ...
This occurs in what is conceived to be a Thl mouse strain, particularly disposed towards inflammatory induction; in other strains of mice of the Th2 type, such as the BALB/c, certain autoimmune diseases are difficult to induce. The nature of the peptide chosen for therapy is an important ingredient: for example, determinants with high affinity for the MHC tend to induce Thl responses.
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From page 38... ...
Preventive Vaccines for Autoimmune Diseases Preventive vaccines for autoimmune diseases are also on the near horizon. Individuals who are genetically susceptible to type I diabetes can be identified now, and quite early in the disease course, when diagnostic antibodies appear to antigens of the islets of Langerhans, tolerance-inducing therapy to insulin or glutamic acid decarboxylase, two major candidate diabetogens, can be introduced.
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