Important note: Information in this article was accurate in 1991. The state of the art may have changed since the publication date.
T-CELL IMMUNITY AND VACCINE ENGINEERING: APPLICATION TO THE AIDS VIRUS
AIDS Vaccine Research and Clinical Trials. Putney SD and Bolognesi DP, eds. New York, Marcel Dekker, p. 139-56, 1990.. Unique Identifier : AIDSLINE ICDB/91676946 Cease KB; Berzofsky JA; Dept. of Internal Medicine, Univ. of Michigan Medical Sch., Ann; Arbor, MI
Abstract:
Protective immunity against the AIDS virus is the goal of all current AIDS vaccine research. However, such an immunity has not been demonstrated in man under any circumstances. The development of a safe and effective vaccine for AIDS clearly is one of the most difficult vaccine challenges in history. The role of T-cell immunity in engineering a vaccine for AIDS is reviewed under the following headings: vaccines and immune protection, experimental design in subunit vaccine development, molecular analysis of the antibody response to HIV, analysis of HIV-specific T-cell responses, T-cell site identification in AIDS virus proteins, and molecular immunology and modern vaccine development. Seven antibody sites with glycoprotein gp160 of HIV have been reported to date: three within gp120 and four within gp41. Six of these have activity in studies using the peptide immunogen, native test antigen design experiments, and at least five have some potential for eliciting neutralizing antibody. The site focused on residues 307-314 appears to be the most promising, although it is in a region of sequence variability among different isolates. Initial work has focused on envelope proteins for several reasons, including the success of this approach in feline and murine retrovirus models. However, it is clear that T-cell responses to internal proteins may be as important as the response to envelope proteins if not more so. Critical internal protein reagents from HIV are increasingly available and will facilitate study of these responses. Understanding the T-cell response to a given antigen at the molecular level is essential to vaccine engineering because it enables the development of highly immunogenic constructs that elicit pathogen-specific T-cell responses and that simultaneously avoid the use of irrelevant carrier protein. This platform of T-cell help then can support the addition of desired B-cell sites or possible cytotoxic T-lymphocyte sites. Sites responsible for undesirable cross-reactions would be excluded by design, whereas conformations that hinder the recognition of other segments must be discovered empirically and engineered out. Such rational vaccine development is being pursued in a number of laboratories and may represent the critical path to a safe and effective AIDS vaccine. (81 Refs)
Keywords: Acquired Immunodeficiency Syndrome/*IMMUNOLOGY/PREVENTION & CONTROL Antigenic Variation/IMMUNOLOGY B-Lymphocytes/IMMUNOLOGY Human HIV/*IMMUNOLOGY HIV Antibodies/BIOSYNTHESIS HIV Antigens/BIOSYNTHESIS T-Lymphocytes/*IMMUNOLOGY Vaccines, Synthetic/*IMMUNOLOGY Viral Vaccines/*IMMUNOLOGY MONOGRAPH REVIEW 912130
M91C4095
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Important note: Information in this article was accurate in 1991. The state of the art may have changed since the publication date.
