Skip to main content

Volume 6 Supplement 3

AIDS Vaccine 2009

  • Oral presentation
  • Open access
  • Published:

OA07-03. Influence of preexisting vaccinia immunity on a DNA/MVA SIV vaccine, decreased cellular immunity but enhanced control of a pathogenic SIV challenge

Background

The influence of preexisting immunity to viral vectors is a major issue for the development of viral vectored vaccines. Here we report that for a DNA/MVA vaccine, preexisting immunity to vaccinia virus (Dryvax) decreases cellular immune responses but enhances control of an intrarectal SIV challenge.

Methods

Three groups of rhesus macaques, eight per group, were studied. The Dryvax-naive and Dryvax-immune groups received the DNA/MVA SIV vaccine (DNA at weeks 0 and 8, and rMVA at weeks 16 and 24). In addition, the Dryvax-immune group received the Dryvax vaccine 1.5 years prior to the DNA prime. The control group did not receive any vaccine. All macaques were challenged intrarectally with SIV251 at 9 months after the final MVA.

Results

Following vaccination, the frequency of SIV Gag-specific CD4 and CD8 T cells were 5–10 fold lower in the Dryvax-immune group than the Dryvax-naive group. Despite their low SIV-specific T cell responses, the Dryvax-immune macaques exhibited the best control of SIV challenge with viremia 480-fold lower at peak and 40-fold lower at set point than in the unvaccinated control animals (p = 0.01). The enhanced control in the Dryvax-immune animals was not restricted to Mamu A*01+ animals and was strongly associated with reduced colorectal virus at 2 weeks post challenge. Factors that correlated with early colorectal viral control included the magnitude of vaccine-elicited CD4 T cells displaying the CCR5 viral co-receptor, which was dampened in the Dryvax-immune animals; the presence of anti-viral mucosal IgA, which was more frequent in the Dryvax-immune animals, and the avidity of the anti-Env Ab response. The frequency of anti-viral CD8 T cells did not correlate with early colorectal viral control.

Conclusion

These results highlight important roles for vaccine-elicited CCR5+ CD4 T cells in augmenting, and mucosal IgA and high avidity anti-Env IgG in restricting the early replication of a colorectal immunodeficiency virus challenge.

Author information

Authors and Affiliations

Authors

Rights and permissions

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 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.

Reprints and permissions

About this article

Cite this article

Kannanganat, S., Nigam, P., Velu, V. et al. OA07-03. Influence of preexisting vaccinia immunity on a DNA/MVA SIV vaccine, decreased cellular immunity but enhanced control of a pathogenic SIV challenge. Retrovirology 6 (Suppl 3), O51 (2009). https://doi.org/10.1186/1742-4690-6-S3-O51

Download citation

  • Published:

  • DOI: https://doi.org/10.1186/1742-4690-6-S3-O51

Keywords