TY - JOUR
T1 - Vaccine induction of antibodies and tissue-resident CD8+ T cells enhances protection against mucosal SHIV-infection in young macaques
AU - Petitdemange, Caroline
AU - Kasturi, Sudhir Pai
AU - Kozlowski, Pamela A.
AU - Nabi, Rafiq
AU - Quarnstrom, Clare F.
AU - Reddy, Pradeep Babu Jagadeesh
AU - Derdeyn, Cynthia A.
AU - Spicer, Lori M.
AU - Patel, Parin
AU - Legere, Traci
AU - Kovalenkov, Yevgeniy O.
AU - Labranche, Celia C.
AU - Villinger, François
AU - Tomai, Mark
AU - Vasilakos, John
AU - Haynes, Barton
AU - Kang, C. Yong
AU - Gibbs, James S.
AU - Yewdell, Jonathan W.
AU - Barouch, Dan
AU - Wrammert, Jens
AU - Montefiori, David
AU - Hunter, Eric
AU - Amara, Rama R.
AU - Masopust, David
AU - Pulendran, Bali
PY - 2019/2/21
Y1 - 2019/2/21
N2 - Antibodies and cytotoxic T cells represent 2 arms of host defense against pathogens. We hypothesized that vaccines that induce both high-magnitude CD8+ T cell responses and antibody responses might confer enhanced protection against HIV. To test this hypothesis, we immunized 3 groups of nonhuman primates: (a) Group 1, which includes sequential immunization regimen involving heterologous viral vectors (HVVs) comprising vesicular stomatitis virus, vaccinia virus, and adenovirus serotype 5-expressing SIVmac239 Gag; (b) Group 2, which includes immunization with a clade C HIV-1 envelope (Env) gp140 protein adjuvanted with nanoparticles containing a TLR7/8 agonist (3M-052); and (c) Group 3, which includes a combination of both regimens. Immunization with HVVs induced very high-magnitude Gag-specific CD8+ T cell responses in blood and tissue-resident CD8+ memory T cells in vaginal mucosa. Immunization with 3M-052 adjuvanted Env protein induced robust and persistent antibody responses and long-lasting innate responses. Despite similar antibody titers in Groups 2 and 3, there was enhanced protection in the younger animals in Group 3, against intravaginal infection with a heterologous SHIV strain. This protection correlated with the magnitude of the serum and vaginal Env-specific antibody titers on the day of challenge. Thus, vaccination strategies that induce both CD8+ T cell and antibody responses can confer enhanced protection against infection.
AB - Antibodies and cytotoxic T cells represent 2 arms of host defense against pathogens. We hypothesized that vaccines that induce both high-magnitude CD8+ T cell responses and antibody responses might confer enhanced protection against HIV. To test this hypothesis, we immunized 3 groups of nonhuman primates: (a) Group 1, which includes sequential immunization regimen involving heterologous viral vectors (HVVs) comprising vesicular stomatitis virus, vaccinia virus, and adenovirus serotype 5-expressing SIVmac239 Gag; (b) Group 2, which includes immunization with a clade C HIV-1 envelope (Env) gp140 protein adjuvanted with nanoparticles containing a TLR7/8 agonist (3M-052); and (c) Group 3, which includes a combination of both regimens. Immunization with HVVs induced very high-magnitude Gag-specific CD8+ T cell responses in blood and tissue-resident CD8+ memory T cells in vaginal mucosa. Immunization with 3M-052 adjuvanted Env protein induced robust and persistent antibody responses and long-lasting innate responses. Despite similar antibody titers in Groups 2 and 3, there was enhanced protection in the younger animals in Group 3, against intravaginal infection with a heterologous SHIV strain. This protection correlated with the magnitude of the serum and vaginal Env-specific antibody titers on the day of challenge. Thus, vaccination strategies that induce both CD8+ T cell and antibody responses can confer enhanced protection against infection.
KW - AIDS vaccine
KW - AIDS/HIV
KW - Adaptive immunity
KW - Vaccines
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U2 - 10.1172/jci.insight.126047
DO - 10.1172/jci.insight.126047
M3 - Article
C2 - 30830870
AN - SCOPUS:85062397900
SN - 2379-3708
VL - 4
JO - JCI Insight
JF - JCI Insight
IS - 4
ER -