- Poster presentation
- Open Access
Optimizing delivery of HIV-1 conserved region-derived immunogen for induction of T and B cell responses in rhesus macaques
© Rosario et al; licensee BioMed Central Ltd. 2012
- Published: 13 September 2012
- Rhesus Macaque
- Vaccine Formulation
- Complex Regimen
- Single Epitope
The complexity of candidate HIV-1 vaccine formulations is increasing due to extreme challenges faced when trying to prevent or control HIV-1 infection.
Immunogen HIVconsv based on the most conserved regions of the HIV-1 proteome was used to explore combinations of seven distinct vaccines modalities in heterologous prime-boost regimens delivered to rhesus macaques to optimize induction of T cell and antibody responses. These include plasmid DNA (P), Semliky Forest virus replicons delivered as DNA (DREP; D) or virus particles (VREP; V), modified vaccinia virus Ankara (MVA; M), adenoviruses of human (HAdV-5; A) and chimpanzee origin (ChAdV-63; C) and adjuvanted synthetic long peptides (SLP; S).
A number of observations were made. Thus, a very potent combination for induction of HIV-1-specific T cells was an adenovirus vector (A or C) followed by poxvirus M. S boost broadened T cell responses, but did not prime T cells efficiently. D was a stronger prime than P. PPP was the best prime for T cells, while PSS was best for induction of antibodies. Even very complex regimen PPPAMSSCMV continued to recruit new T cell clones into the response to a single epitope, although a ceiling for immunodominant responses was reached; subdominant responses could be boosted up to the last V delivery. Finally, PPSS, but not SSSS could protect 2/6 animals from SIVmac251 acquisition.
These results will guide initial design of human trials. So far, human studies in Oxford testing CM, PPPCM and PPPMC regimen concur with observations made in rhesus macaques.
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.