Signature for long-term vaccine-mediated control of a Simian and human immunodeficiency virus 89.6P challenge: stable low-breadth and low-frequency T-cell response capable of coproducing gamma interferon and interleukin-2.
In 2001, we reported 20 weeks of control of challenge with the virulent 89.6P chimera of simian and human immunodeficiency viruses (SHIV-89.6P) by a Gag-Pol-Env vaccine consisting of DNA priming and modified vaccinia virus Ankara boosting. Here we report that 22 out of 23 of these animals successfully controlled their viremia until their time of euthanasia at 200 weeks postchallenge. At euthanasia, all animals had low to undetectable viral loads and normal CD4 counts. During the long period of viral control, gamma interferon (IFN-gamma)-producing antiviral T cells were present at unexpectedly low breadths and frequencies. Most animals recognized two CD8 and one CD4 epitope and had frequencies of IFN-gamma-responding T cells from 0.01 to 0.3% of total CD8 or CD4 T cells. T-cell responses were remarkably stable over time and, unlike responses in most immunodeficiency virus infections, maintained good functional characteristics, as evidenced by coproduction of IFN-gamma and interleukin-2. Overall, high titers of binding and neutralizing antibody persisted throughout the postchallenge period. Encouragingly, long-term control was effective in macaques of diverse histocompatibility types.
Sadagopal
Shanmugalakshmi
S
Yerkes National Primate Research Center of Emory University, 954 Gatewood Dr., Atlanta, GA 30329, USA.
Amara
Rama Rao
RR
Montefiori
David C
DC
Wyatt
Linda S
LS
Staprans
Silvija I
SI
Kozyr
Natalia L
NL
McClure
Harold M
HM
Moss
Bernard
B
Robinson
Harriet L
HL
D016915:AIDS Vaccines / Q000276:immunology*; D000818:Animals; D018791:CD4 Lymphocyte Count; D004195:Disease Models, Animal; D000939:Epitopes / Q000276:immunology; D015686:Gene Products, env / Q000276:immunology; D015683:Gene Products, gag / Q000276:immunology; D015684:Gene Products, pol / Q000276:immunology; D006678:HIV / Q000235:genetics / Q000254:growth & development / Q000276:immunology*; D007371:Interferon-gamma / Q000096:biosynthesis*; D007376:Interleukin-2 / Q000096:biosynthesis*; D008251:Macaca; D012367:RNA, Viral / Q000097:blood; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology*; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000254:growth & development / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D019444:Vaccines, DNA / Q000276:immunology; D014616:Vaccinia virus / Q000235:genetics / Q000276:immunology; D019562:Viral Load; D014766:Viremia / Q000276:immunology
D016915:AIDS Vaccines; D000939:Epitopes; D015686:Gene Products, env; D015683:Gene Products, gag; D015684:Gene Products, pol; D007376:Interleukin-2; D012367:RNA, Viral; D019444:Vaccines, DNA; D007371:Interferon-gamma
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