Rapid SIV Env-specific mucosal and serum antibody induction augments cellular immunity in protecting immunized, elite-controller macaques against high dose heterologous SIV challenge.
Three Indian rhesus macaques, Ad-SIV primed/protein boosted and exposed twice to high-dose mucosal SIV(mac251) 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 SIV(smE660), 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 SIV(smE660) challenge. Initial vaccine-induced control by macaque #5 extended to the SIV(smE660) challenge due to multiple immune mechanisms that were boosted and augmented by cryptic SIV exposure.
Vaccine Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
L Jean
LJ
Patterson
Mara
M
Daltabuit-Test
Peng
P
Xiao
Jun
J
Zhao
William
W
Hu
Ulrike
U
Wille-Reece
Egidio
E
Brocca-Cofano
V S
VS
Kalyanaraman
Irene
I
Kalisz
Stephen
S
Whitney
Eun Mi
EM
Lee
Ranajit
R
Pal
David C
DC
Montefiori
Satya
S
Dandekar
Robert
R
Seder
Mario
M
Roederer
Roger W
RW
Wiseman
Vanessa
V
Hirsch
Marjorie
M
Robert-Guroff
D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology; D000914:Antibodies, Viral / Q000276:immunology*; D007111:Immunity, Cellular; D018928:Immunity, Mucosal; D007583:Jejunum / Q000821:virology; D008198:Lymph Nodes / Q000821:virology; D008253:Macaca mulatta; D044967:Serum / Q000276:immunology; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000517:prevention & control*; D015302:Simian Immunodeficiency Virus / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D014766:Viremia / Q000517:prevention & control
D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral
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