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Published on: April 22, 2010
Immunization against SIVmne in macaques using multigenic DNA vaccines
S P Mossman1, C C Pierce, M N Robertson
1Seattle Biomedical Research Institute, WA 98109-1651, USA.
Abstract:
All structural and regulatory genes of SIVmne were cloned into mammalian expression vectors to optimize expression in vitro and immunogenicity in mice. Macaca fascicularis were immunized four times with plasmid DNA (n = 4), or two DNA priming inoculations followed by two boosts of recombinant gp160 plus Gag-Pol particles (n = 4). Following intrarectal challenge with SIVmne, all macaques became infected. Three monkeys immunized with DNA alone maintained low plasma virus loads by 1 year post-challenge; the fourth exhibited high virus loads and significant CD4+ cell decline. Two of the DNA plus boost and three control macaques had high virus loads and associated CD4+ cell decline. Both vaccine protocols elicited antibodies and comparable helper T-cell proliferative responses to gp160. Cytokine mRNA levels in activated peripheral blood mononuclear cells (PBMC) taken at time of challenge suggested a dominant T helper (Th) 1 state in three DNA-immunized and one protein-boosted macaque, which correlated with low virus loads and high CD4+ cell counts post-challenge.
Insights
DNA vaccination strategies for simian immunodeficiency virus (SIV) in macaques showed partial success. Some DNA-vaccinated monkeys controlled virus loads, correlating with a T helper 1 immune response.
Area of Science:
- Immunology
- Virology
- Vaccine Development
Background:
- Simian immunodeficiency virus (SIV) infection in macaques serves as a model for human immunodeficiency virus (HIV) research.
- Developing effective vaccines against SIV is crucial for advancing HIV vaccine strategies.
Purpose of the Study:
- To evaluate the immunogenicity and efficacy of DNA-based vaccines against SIV in a macaque model.
- To assess the correlation between immune responses and viral control post-challenge.
Main Methods:
- Cloning of SIVmne genes into expression vectors for in vitro and in vivo studies.
- Immunization of macaques (Macaca fascicularis) with plasmid DNA or DNA prime-boosted with recombinant gp160 plus Gag-Pol particles.
- Intrarectal challenge with SIVmne and monitoring of viral loads and CD4+ T-cell counts.
Main Results:
- All vaccinated and control macaques became infected post-challenge.
- Three out of four DNA-vaccinated macaques maintained low viral loads and CD4+ cell counts one year post-infection.
- Both vaccine protocols induced antibodies and T-cell responses to gp160.
- A dominant T helper 1 (Th1) cytokine profile in peripheral blood mononuclear cells (PBMC) correlated with better viral control.
Conclusions:
- DNA vaccination strategies can elicit immune responses and partially control SIV replication in macaques.
- A Th1-biased immune response appears critical for controlling SIV infection post-vaccination.
- Further optimization of SIV vaccine approaches is warranted.
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