Vaccine-induced cellular immunity can control viral replication in simian immunodeficiency virus (SIV)-infected monkeys, though the level and persistence of viral control is not optimal. We previously demonstrated that immunization of monkeys with plasmid DNA followed by replication defective adenoviral vectors encoding SIV proteins led to a reduction in viremia and prolonged survival. This survival was associated with preserved central memory CD4+ T lymphocytes and could be predicted by the magnitude of the vaccine-induced cellular immune response. These immune correlates of vaccine efficacy should guide the evaluation of AIDS vaccines in humans. In addition, the results of the this study indicated that set point viral load and total CD4+ T lymphocyte count may not be fully predictive of a vaccine effect. ? ? The studies described above used a combination of several SIV antigens: Env, Gag and Pol. In an ongoing study, we immunized monkeys with this same combination, or with Env alone, or Gag-Pol alone, to determine the individual effect of each vaccine immunogen. The results indicate that both Gag-Pol and Env contribute to a protective effect on viral load and that these effects are most likely T-cell mediated. The combination of Env plus Gag-Pol worked better than either alone. Other ongoing studies will test the effect of several alternative serotypes of recombinant adenovirus? ? In addition, we are currently performing studies to develop a low dose mucosal challenge model for SIV - which may be a more physiological model of human HIV infection

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Intramural Research (Z01)
Project #
1Z01AI005009-07
Application #
7732732
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
7
Fiscal Year
2008
Total Cost
$305,129
Indirect Cost
City
State
Country
United States
Zip Code
Keele, Brandon F; Li, Hui; Learn, Gerald H et al. (2009) Low-dose rectal inoculation of rhesus macaques by SIVsmE660 or SIVmac251 recapitulates human mucosal infection by HIV-1. J Exp Med 206:1117-34
Whitney, James B; Luedemann, Corinne; Hraber, Peter et al. (2009) T-cell vaccination reduces simian immunodeficiency virus levels in semen. J Virol 83:10840-3
Letvin, Norman L; Rao, Srini S; Dang, Vi et al. (2007) No evidence for consistent virus-specific immunity in simian immunodeficiency virus-exposed, uninfected rhesus monkeys. J Virol 81:12368-74
Letvin, Norman L; Mascola, John R; Sun, Yue et al. (2006) Preserved CD4+ central memory T cells and survival in vaccinated SIV-challenged monkeys. Science 312:1530-3
Sun, Yue; Schmitz, Jorn E; Buzby, Adam P et al. (2006) Virus-specific cellular immune correlates of survival in vaccinated monkeys after simian immunodeficiency virus challenge. J Virol 80:10950-6
Acierno, Paula M; Schmitz, Jorn E; Gorgone, Darci A et al. (2006) Preservation of functional virus-specific memory CD8+ T lymphocytes in vaccinated, simian human immunodeficiency virus-infected rhesus monkeys. J Immunol 176:5338-45
Seaman, Michael S; Santra, Sampa; Newberg, Michael H et al. (2005) Vaccine-elicited memory cytotoxic T lymphocytes contribute to Mamu-A*01-associated control of simian/human immunodeficiency virus 89.6P replication in rhesus monkeys. J Virol 79:4580-8
Mascola, John R; Sambor, Anna; Beaudry, Kristin et al. (2005) Neutralizing antibodies elicited by immunization of monkeys with DNA plasmids and recombinant adenoviral vectors expressing human immunodeficiency virus type 1 proteins. J Virol 79:771-9
Sun, Yue; Schmitz, Jorn E; Acierno, Paula M et al. (2005) Dysfunction of simian immunodeficiency virus/simian human immunodeficiency virus-induced IL-2 expression by central memory CD4+ T lymphocytes. J Immunol 174:4753-60
Zhang, Lei; Ribeiro, Ruy M; Mascola, John R et al. (2004) Effects of antibody on viral kinetics in simian/human immunodeficiency virus infection: implications for vaccination. J Virol 78:5520-2

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