Rapid SIV Env-specific mucosal and serum antibody induction augments cellular immunity in protecting immunized, elite-controller macaques against high dose heterologous SIV challenge

Abstract Three Indian rhesus macaques, Ad-SIV primed/protein boosted and exposed twice to high-dose mucosal SIVmac251 challenges, exhibited elite control of viremia over 6.5 years. They were negative for host factors associated with control of SIV infection. After a third intrarectal challenge with...

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Veröffentlicht in:Virology (New York, N.Y.) N.Y.), 2011-03, Vol.411 (1), p.87-102
Hauptverfasser: Patterson, L. Jean, Daltabuit-Test, Mara, Xiao, Peng, Zhao, Jun, Hu, William, Wille-Reece, Ulrike, Brocca-Cofano, Egidio, Kalyanaraman, V.S, Kalisz, Irene, Whitney, Stephen, Lee, Eun Mi, Pal, Ranajit, Montefiori, David C, Dandekar, Satya, Seder, Robert, Roederer, Mario, Wiseman, Roger W, Hirsch, Vanessa, Robert-Guroff, Marjorie
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Sprache:eng
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Zusammenfassung:Abstract Three Indian rhesus macaques, Ad-SIV primed/protein boosted and exposed twice to high-dose mucosal SIVmac251 challenges, exhibited elite control of viremia over 6.5 years. They were negative for host factors associated with control of SIV infection. After a third intrarectal challenge with SIVsmE660 , all controlled viremia, with one (macaque #5) maintaining undetectable viremia in blood. Acquisition was not blocked, but virus was contained in the jejunum and draining lymph nodes. Polyfunctional memory T cell responses and high-titered neutralizing and non-neutralizing serum and mucosal antibodies were present before and maintained post-challenge. The level of protection seen for animal #5 was predicted from analyses of gene transcription in jejunum 2 weeks post-challenge. Macaques #7 and #9, exhibiting lower pre-challenge cellular and humoral immunity, partially controlled the SIVsmE660 challenge. Initial vaccine-induced control by macaque #5 extended to the SIVsmE660 challenge due to multiple immune mechanisms that were boosted and augmented by cryptic SIV exposure.
ISSN:0042-6822
1096-0341
DOI:10.1016/j.virol.2010.12.033