Comparative Efficacy of Subtype AE Simian-Human Immunodeficiency Virus Priming and Boosting Vaccines in Pigtail Macaques
Open Access
- 1 January 2007
- journal article
- research article
- Published by American Society for Microbiology in Journal of Virology
- Vol. 81 (1) , 292-300
- https://doi.org/10.1128/jvi.01727-06
Abstract
Vaccination against AIDS is hampered by great diversity between human immunodeficiency virus (HIV) strains. Heterologous B-subtype-based simian-human immunodeficiency virus (SHIV) DNA prime and poxvirus boost vaccine regimens can induce partial, T-cell-mediated, protective immunity in macaques. We analyzed a set of DNA, recombinant fowlpox viruses (FPV), and vaccinia viruses (VV) expressing subtype AE HIV type 1 (HIV-1) Tat, Rev, and Env proteins and SIV Gag/Pol in 30 pigtail macaques. SIV Gag-specific CD4 and CD8 T-cell responses were induced by sequential DNA/FPV vaccination, although lower FPV doses, VV/FPV vaccination, and DNA vaccines alone were not as consistently immunogenic. The SHIV AE DNA prime, FPV boost regimens were significantly less immunogenic than comparable B-subtype SHIV vaccination. Peak viral load was modestly (0.4 log 10 copies/ml) lower among the AE subtype SHIV-immunized animals compared to controls following the virulent B subtype SHIV challenge. Protection from persistent high levels of viremia and CD4 T-cell depletion was less in AE subtype compared to B subtype SHIV-vaccinated macaques. Gag was highly immunodominant over the other AE subtype SHIV vaccine proteins after vaccination, and this immunodominance was exacerbated after challenge. Interestingly, the lower level of priming of immune responses did not blunt postchallenge Gag-specific recall responses, despite more modest protection. These studies suggest priming of T-cell immunity to prevent AIDS in humans is possible, but differences in the immunogenicity of various subtype vaccines and broad cross-subtype protection are substantial hurdles.Keywords
This publication has 26 references indexed in Scilit:
- Vaccine-Induced Cellular Immune Responses Reduce Plasma Viral Concentrations after Repeated Low-Dose Challenge with Pathogenic Simian Immunodeficiency Virus SIVmac239Journal of Virology, 2006
- Comparative Evaluation of Simian, Simian–Human, and Human Immunodeficiency Virus Infections in the Pigtail Macaque (Macaca nemestrina) ModelAIDS Research and Human Retroviruses, 2006
- Fowlpox virus vaccines for HIV and SHIV clinical and pre-clinical trialsVaccine, 2006
- The pigtail macaque MHC class I allele Mane‐A*10 presents an immundominant SIV Gag epitope: identification, tetramer development and implications of immune escape and reversionJournal of Medical Primatology, 2005
- Mucosally-administered human–simian immunodeficiency virus DNA and fowlpoxvirus-based recombinant vaccines reduce acute phase viral replication in macaques following vaginal challenge with CCR5-tropic SHIVSF162P3Vaccine, 2005
- Subtype AE HIV-1 DNA and recombinant Fowlpoxvirus vaccines encoding five shared HIV-1 genes: safety and T cell immunogenicity in macaquesVaccine, 2005
- Analysis of Pigtail Macaque Major Histocompatibility Complex Class I Molecules Presenting Immunodominant Simian Immunodeficiency Virus EpitopesJournal of Virology, 2005
- Efficacy of DNA and Fowlpox Virus Priming/Boosting Vaccines for Simian/Human Immunodeficiency VirusJournal of Virology, 2004
- Evaluation in macaques of HIV-1 DNA vaccines containing primate CpG motifs and fowlpoxvirus vaccines co-expressing IFN? or IL-12Vaccine, 2004
- Immunization of Rhesus Macaques with a DNA Prime/Modified Vaccinia Virus Ankara Boost Regimen Induces Broad Simian Immunodeficiency Virus (SIV)-Specific T-Cell Responses and Reduces Initial Viral Replication but Does Not Prevent Disease Progression following Challenge with Pathogenic SIVmac239Journal of Virology, 2002