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Humoral and cellular immunities elicited by HIV-1 vaccination
J W Shiver1, M E Davies, H C Perry
1Department of Virus and Cell Biology, Merck Research Laboratories, West Point, PA 19486, USA.
Journal of Pharmaceutical Sciences
|December 1, 1996
Summary
DNA vaccines encoding HIV-1 proteins induced robust, long-lasting humoral and cellular immune responses in mice and nonhuman primates. These findings highlight plasmid DNA
Area of Science:
- Immunology
- Vaccinology
- Molecular Biology
Background:
- Plasmid DNA immunization can induce immune responses against viral antigens.
- HIV-1 envelope glycoprotein 120 (gp120) and rev proteins are key targets for vaccine development.
Purpose of the Study:
- To evaluate the efficacy of plasmid DNA vaccines expressing HIV-1 gp120 or rev proteins in eliciting immune responses.
- To assess both humoral and cellular immunity induced by these DNA vaccines in preclinical models.
Main Methods:
- Mice and nonhuman primates were intramuscularly injected with plasmids encoding tPA-gp120 or rev.
- Humoral responses were measured by ELISA for antibody production.
- Cellular responses were assessed via splenocyte proliferation, cytotoxic T lymphocyte (CTL) activity, and cytokine profiling (gamma-interferon, IL-4).
Main Results:
- DNA vaccination elicited antigen-specific antibody responses against HIV-1 gp120 and V2 peptide neutralization epitope.
- Vaccinated animals showed gp120-specific T cell proliferation and MHC Class I-restricted CTL activity.
- Primarily T helper 1 (Th1)-like responses were induced, characterized by high gamma-interferon production.
- Immune responses were dose-dependent, boostable, and persisted for over six months.
- Nonhuman primates developed neutralizing antibodies against HIV.
Conclusions:
- Plasmid DNA vaccines effectively induce significant humoral and cellular immune responses against HIV-1 antigens.
- The induced immune responses are characterized by a Th1-like profile and are long-lived.
- DNA vaccination represents a promising strategy for developing an effective HIV vaccine.