Human vaccination

Adjuvants are substances which can modify the immune response of an antigen (139,140). With better understanding of the functions of different arms of the immune system, it is possible to explore the effects of an adjuvant, such that the protective efficacy of a vaccine can be improved. At present, aluminum salt is the only adjuvant approved for use in human vaccines. New adjuvants such as QS-21, 3D-MPL, MF-59, and other liposome preparations are being evaluated. Several of these adjuvants have been in clinical trial, but none have been approved for human use. IL-12 has been proposed as an adjuvant which can specifically promote T-helper 1 ceU response, and can be a very promising adjuvant for future vaccine development. 

Biologicals. Figure 4 Licensed human vaccines. From Immunity Immune Response in Inflammatory Disease by DeFranco, Locksley and Robertson [2]. 

Table 15.1 Bacterial vaccines used for the prevention of infectious disease in humans. Vaccines marked are those used in conventionai immunization scheduies those marked f are used to provide additionai protection when circumstances indicate a need... 

Lettuce, spinach Edible, useful for human vaccines Low protein stability in harvested material... 

Saponins are a family of glycosides (sugar derivatives) widely distributed in plants. Each saponin consists of a sugar moiety bound to a sapogenin (either a steroid or a triterpene). The immunostimulatory properties of the saponin fraction isolated from the bark of Quillaja (a tree) has been long recognized. Quil A (which consists of a mixture of related saponins) is used as an adjuvant in selected veterinary vaccines. However, its haemolytic potential precludes its use in human vaccines. Research efforts continue in an attempt to identify individual saponins (or derivatives thereof) that would make safe and effective adjuvants for use in human medicine. 

Vaccines No approved human vaccine is available in the United States. Killed and live attenuated human vaccines have been available in many countries, but are considered of unproven efficacy within the United States. 

The recommended treatment is doxycycline (200 mg/day) plus rifampin (600 mg/day) for six weeks. An alternative effective treatment is six weeks of doxycycline (200 mg/day) plus streptomycin (1 gm/day) for three weeks. Trimethoprim-sulfamethoxazole given four to six weeks is less effective. In 5 to f 0 percent of cases, there may be a relapse or treatment failure. Regarding prophylaxis, killed and live attenuated human vaccines are available in many countries but are considered of unproven efficacy. There tends to be no information on the use of antibiotics for prophylaxis against human brucellosis. 

Vaccines There is no human vaccine available for brucellosis, although there are a number animal vaccines since this disease is one of the most important veterinary diseases in the entire world. 

Vaccines There is currently no human vaccine available to prevent SEB intoxication. One has been under development since 1996. Be certain to wear a protective mask when dealing with patients. 

Although it is one of the most potent adjuvant substances known, FCA is too toxic for human use. Some of its reported side effects are listed in Table 10.21. Its toxicity has also precluded its routine veterinary application, although it is sometimes used for experimental purposes. FIA is less toxic than its mycobacterial-containing counterpart. It has found used in the preparation of selected animal vaccines, and was even incorporated into some earlier human vaccines (Table 10.22). However, its use in humans (and to a large extent, animals) has been discontinued due to its reported toxic effects. 

Gupta, R. Siber, G. (1995). Adjuvants for human vaccines — current status, problems and future prospects. Vaccine 13(14), 1263-1274. 

Sandhu, J. (1994). Engineered human vaccines. Crit. Rev. Biotechnol. 14(1), 1-27. 

Dick Jr WE, Beurret M (1989) Glycoconjugates of bacterial carbohydrate antigens. In Cruse JM, Lewis Jr RE (eds) Contrib Microbiol Immunol. Karger, Basel, vol 10, p 48 Jennings HJ, Sood RK (1994) Synthetic giycoconjugates as human vaccines. In Lee YC, Lee RT (eds) Neoglycoconjugates preparation and applications. Academic Press, San Diego, p 325... 

Chlorogen, Inc. Virginia St. Louis, Human vaccines Tobacco... 

Ott, G, G.L. Barchfeld, D. Chernoff, R. Radhakrishnan, P. van Hoogevest, and G. Van Nest, MF59. Design and evaluation of a safe and potent adjuvant for human vaccines. Pharm Biotechnol, 1995. 6 277-96. 

Gluck, R., Liposomal presentation of antigens for human vaccines. Rharm Biotech-nol, 1995. 6 325-45. 

Ott G, Barchfeld GL, Chernoff D, Radhakrishnan R, van Hoogevest P, Van Nest G. MF59 design and evaluation of a safe and potent adjuvant for human vaccines. In Powell MF, Newman MJ, eds. Vaccine Design The Subunit and Adjuvant Approach. New York Plenum Press, 1995 277-296. 

Jenner performs the first successful human vaccination against smallpox. 

Jennings HJ, Sood RK (1994) Synthetic glycoconjugates as human vaccines. In Lee YC, Lee RT (eds) Neoglycoconjugates preparation and applications. Academic Press, San Diego, p 325... 

Adjuvants. Adjuvants are substances which can modify the immune response of an antigen. With better understanding of the functions of different aims of the immune system, it is possible to explore the effects of an adjuvant, such that the protective efficacy of a vaccine can be improved. At present, aluminum salt is the only adjuvant approved for use in human vaccines. 

As schistosomes are long-lived and pre-pubertal children show little evidence of acquired immunity, can protection be reliably achieved in a permissive host Experiments in rodents and primates with cercariae attenuated by radiation provide an emphatic yes in answer to this question. Over a 40-year-period, many laboratories have reproducibly obtained a 60-70% reduction in worm burden after a single vaccination of high responder mouse strains. The attenuated vaccine model has been extensively investigated as a paradigm for a human vaccine (reviewed by Coulson, 1997) and the salient features are summarized below. 

Another major variable affecting vaccination success is the way in which an antigen is formulated and the conditions under which it is presented. This is well illustrated by the coadministration of recombinant IL-12 with the highly effective attenuated vaccine, which enhances the cell-mediated arm of the immune response and boosts protection levels to >90% (Wynn ef a/., 1995 Mountford ef a/., 1996). Replicated in a human vaccine, such an outcome would have a dramatic effect on morbidity and transmission. 

Coulson, P.S. (1997) The radiation-attenuated vaccine against schistosomes in animal models paradigm for a human vaccine Advances in Parasitology 39, 271-336. 

The United States Food and Dmg Administration approves the first genetically engineered human vaccine for hepatitis B. 

Kawakita, 1963). This cell line is certified by the WHO (World Health Organization) and is usually employed for virus propagation (polio, rabies) for human vaccine production. Another important application of these cells is in cytotoxicity studies of biomaterials projected for repairing or reconstituting injured human tissues. 

Huvax www.violinet. org/huvax Licensed human vaccines... 

Because licensed vaccines are the focus of much attention in the public as well as in the vaccine research community, VIOLIN has two subdatabases that focus on licensed human and animal vaccines. The Huvax subdatabase (http //www.violinet.org/huvax) stores all licensed human vaccines in the USA and Canada. The data for these licensed human vaccines are annotated through manual curation and a vigorous review process. Huvax includes manually curated data including manufacturer, trade name, storage information, age at which the vaccine should be administered, and other relevant information. These vaccines are also listed by the CDC CVX codes (codes that indicate the product used in a vaccine) for tracking vaccination records. Huvax has provided cross-references based on these CDC CVX codes. Huvax provides ways for users to search, compare, and analyze licensed human vaccines. Various criteria can be used for querying human vaccines. Different vaccines can also be compared side by side. Vevax is a VIOLIN database of licensed veterinary vaccines (http //www. violinet.org/vevax). 

Attenuated pentavalent bovine-human vaccine contains human rotavirus genes from each serotype ... 

Dale, P.A. McQuillen, D.P., Gulati, S., Rice, P.A. Human vaccination with Escherichia coli 35 mutant induces cross-reactive bactericidal antibody against Neisseria gonorrhoeae lipooligosaccharide. J Infect Dis 166 (1992) 316. 

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