Amara R, Smith J, Villinger F, Altman J, Staprans S, Kozyr N, Lydy S, Robinson H.
AIDS Vaccine 2001. 2001 Sep 5-8; abstract no. 165.
Emory Univ., Atlanta, GA, USA
BACKGROUND: We have recently shown that a multi-protein DNA/MVA vaccine can control a pathogenic SHIV89.6p mucosal challenge. This experiment is designed to look at the requirement of envelope in the vaccine.METHODS: The DNA and MVA components of the vaccine-expressed Gag,Pol or Gag,Pol,Env proteins from the SHIV-89.6 chimera of simian and human immunodeficiency viruses. Two DNA immunizations (at weeks 0 and 8) followed by a single rMVA booster (at week 24) were administered. Two doses (2.5 mg and 250 mug) of DNA priming were tested. The highly pathogenic SHIV-89.6P challenge virus was administered intrarectally at 7 months after the booster immunization, a time when vaccine responses were in memory. CD4 as well as CD8 T-cell responses were quantitated using tetramer analysis, IFN-gamma ELISPOTs, and intracellular cytokine analysis. Antibody responses to Gag and Env were also measured. Post challenge viral RNA copies in plasma were measured using quantitative real-time PCR assay.RESULTS: The DNA/MVA prime-boost protocol raised high frequencies of multi-epitope-specific anti-viral CD4 as well as CD8 T cells in rhesus macaques with diverse histocompatibility types. Post vaccine gag-specific humoral and cellular responses were comparable for Gag-Pol and Gag-Pol-Env groups. The challenge infected all of the vaccine as well as the control animals. Nonvaccinated control animals experienced rapid CD4 loss and 5 out of the 6 nonvaccinated controls succumbed to AIDS by 30 weeks post challenge. Gag-Pol-Env vaccine groups actively contained the virus between weeks 2 and 3 post challenge. By 8 weeks post challenge, all of these animals (12/12) had virus loads at or below detection. These animals were protected against the loss of CD4 cells, destruction of lymph node architecture and rapid onset of AIDS. In contrast, the majority of the Gag-Pol vaccinated animals (8/12) had viral loads greater than 1,000 copies of RNA. These animals also experienced rapid CD4 loss by 2 to 5 weeks post challenge. By 20 weeks post challenge these animals exhibited a moderate recovery from CD4 loss without significant changes in their plasma viral loads. This recovery was associated with an initial burst of anti-viral CD8 T cells followed by the emergence of neutralizing antibodies.CONCLUSIONS: Our results stress the requirement of anti-Env immune response for efficient containment of a pathogenic immunodeficiency virus challenge and the need for inclusion of envelope in AIDS vaccines.
Publication Types:
Keywords:
- AIDS Vaccines
- Acquired Immunodeficiency Syndrome
- CD4-Positive T-Lymphocytes
- CD8-Positive T-Lymphocytes
- Gene Products, env
- Genes, env
- Genes, gag
- Genes, pol
- HIV
- HIV Antibodies
- HIV Infections
- Humans
- Immunization, Secondary
- Macaca mulatta
- Simian Acquired Immunodeficiency Syndrome
- Viral Load
- genetics
Other ID:
UI: 102249434
From Meeting Abstracts