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Volume 6 Supplement 3

AIDS Vaccine 2009

P17-20. Lentiviral vector-based vaccine against SIV infection and simian AIDS

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Background

AIDS vaccination has a pressing need for more potent vaccination vectors capable of eliciting strong, diversified and long-lasting cellular immune responses against HIV. Lentiviral vectors have a proven efficiency not only as gene delivery vehicles for gene therapy applications but also as vaccination tools. This is likely due to their ability to transduce non-dividing cells, including dendritic cells, enabling a sustained endogenous antigen presentation and thus the induction of high proportions of specific cytotoxic T cells and long-lasting memory T cells.

Methods

The protective efficacy of a lentiviral vector based vaccine was assessed in the SIVmac251/cynomolgus macaques model.

Results

Our prime-boost vaccination strategy using lentiviral vectors pseudotyped with a glycoprotein G from two non-cross-reactive VSV serotypes elicited robust and broad cellular immune responses against the vector-encoded antigen, SIV GAG. Vaccination conferred strong protection against a massive intra-rectal challenge with SIVmac251 as evidenced both by the reduction of viremia at the peak of primo-infection (a mean of over 2 log10 fold reduction) and the full preservation of the central memory CD4+ T cells during the acute phase. Although vaccinees continued to display lower viremia than control macaques during the early chronic phase, these differences were not statistically significant by day 50 post-challenge. This encouraging pilot prophylactic trial gave the proof-of concept for the strong potential of the lentiviral vector system for vaccination. Various optimizations were successfully tested in mice to increase the immunogenicity of our vaccine. An improved vaccine – with a codon-optimized sequence encoding 2 viral antigens, GAG together with NEF, under the control of a promoter devoid of associated enhancer activity and injected via the intramuscular route – is being evaluated in a therapeutic setting, in viremic rhesus monkeys.

Conclusion

Gene transfer vectors derived from HIV-1 appear as promising candidates for vaccination against HIV-1 infection.

Author information

Correspondence to A Beignon.

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Open Access This article is published under license to BioMed Central Ltd. This is an Open Access article is distributed under the terms of the Creative Commons Attribution 2.0 International License (https://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Beignon, A., Mollier, K., Liard, C. et al. P17-20. Lentiviral vector-based vaccine against SIV infection and simian AIDS. Retrovirology 6, P302 (2009). https://doi.org/10.1186/1742-4690-6-S3-P302

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Keywords

  • Gene Therapy Application
  • Gene Delivery Vehicle
  • Early Chronic Phase
  • Potent Vaccination
  • Prophylactic Trial