Vaccine induction of antibodies and tissue-resident CD8⁺ T cells enhances protection against mucosal SHIV-infection in young macaques

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Abstract

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.

Authors

Caroline Petitdemange, Sudhir Pai Kasturi, Pamela A. Kozlowski, Rafiq Nabi, Clare F. Quarnstrom, Pradeep Babu Jagadeesh Reddy, Cynthia A. Derdeyn, Lori M. Spicer, Parin Patel, Traci Legere, Yevgeniy O. Kovalenkov, Celia C. Labranche, François Villinger, Mark Tomai, John Vasilakos, Barton Haynes, C. Yong Kang, James S. Gibbs, Jonathan W. Yewdell, Dan Barouch, Jens Wrammert, David Montefiori, Eric Hunter, Rama R. Amara, David Masopust, Bali Pulendran