Studies using a viral challenge and CD8 T cell depletions on the roles of cellular and humoral immunity in the control of an SHIV-89.6P challenge in DNA/MVA-vaccinated macaques.
Here, we study immune responses in four DNA/MVA-vaccinated macaques following an SHIV-89.6P challenge and a subsequent CD8 cell depletion. Both post-challenge and post-depletion peaks of viremia contracted with the expansion, or re-emergence, of CD8 T cells. Post-depletion, CD8 cells expanded in the presence of higher levels of neutralizing Ab and CD4 help than post-challenge and had superior maturational characteristics as measured by expression of the anti-apoptotic protein Bcl-2, the IL-7 receptor CD127 and co-production of IFN-gamma and IL-2. Pre-challenge and pre-depletion titers of neutralizing Ab correlated inversely with peaks of viremia and directly with peaks for anti-viral CD4 cells. Thus, our results reveal CD8 cells playing a central role, and neutralizing Ab, a supporting role in SHIV-89.6P control. They also suggest a dynamic relationship between neutralizing Ab, antigen load and anti-viral CD4 cells in the maturation of high-quality anti-viral CD8 T cells.
Amara
Rama Rao
RR
Emory Vaccine Center, Emory University, Atlanta, GA 30329, USA. rama@rmy.emory.edu
Ibegbu
Chris
C
Villinger
Francois
F
Montefiori
David C
DC
Sharma
Sunita
S
Nigam
Pragati
P
Xu
Yongxian
Y
McClure
Harold M
HM
Robinson
Harriet L
HL
D016915:AIDS Vaccines / Q000494:pharmacology*; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002678:Chimera / Q000276:immunology; D015683:Gene Products, gag / Q000276:immunology; D006678:HIV / Q000276:immunology; D015658:HIV Infections / Q000276:immunology / Q000517:prevention & control; D006801:Humans; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D008212:Lymphocyte Depletion; D008253:Macaca mulatta; D018449:SAIDS Vaccines / Q000494:pharmacology*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000517:prevention & control; D015302:Simian Immunodeficiency Virus / Q000276:immunology; D013997:Time Factors; D019444:Vaccines, DNA / Q000494:pharmacology*; D014766:Viremia / Q000276:immunology
D016915:AIDS Vaccines; D015683:Gene Products, gag; D007376:Interleukin-2; D018449:SAIDS Vaccines; D019444:Vaccines, DNA; D007371:Interferon-gamma