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

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

doi:10.1172/jci.insight.126047

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

JCI Insight. 2019 Feb 21;4(4):e126047. doi: 10.1172/jci.insight.126047.

Authors

Caroline Petitdemange¹, Sudhir Pai Kasturi¹, Pamela A Kozlowski², Rafiq Nabi², Clare F Quarnstrom³, Pradeep Babu Jagadeesh Reddy¹, Cynthia A Derdeyn⁴, Lori M Spicer⁴, Parin Patel¹, Traci Legere¹, Yevgeniy O Kovalenkov⁵, Celia C Labranche⁶, François Villinger⁷, Mark Tomai⁸, John Vasilakos⁸, Barton Haynes⁶, C Yong Kang⁹, James S Gibbs¹⁰, Jonathan W Yewdell¹⁰, Dan Barouch¹¹, Jens Wrammert⁵, David Montefiori⁶, Eric Hunter¹, Rama R Amara¹, David Masopust³, Bali Pulendran¹²

Affiliations

¹ Emory Vaccine Center, Yerkes National Primate Research Center at Emory University, Atlanta, Georgia, USA.
² Department of Microbiology, Immunology, and Parasitology, Louisiana State University Health Sciences Center, New Orleans, Louisiana, USA.
³ Department of Microbiology and Immunology, Center for Immunology, University of Minnesota, Minneapolis, Minnesota, USA.
⁴ Department of Pathology and Laboratory Medicine, Emory Vaccine Center, and Yerkes National Primate Research Center.
⁵ Emory Vaccine Center, School of Medicine, Emory University, Atlanta, Georgia, USA.
⁶ Duke Human Vaccine Institute, Duke University School of Medicine, Durham, North Carolina, USA.
⁷ New Iberia Research Center, University of Louisiana Lafayette, Lafayette, Louisiana, USA.
⁸ 3M Drug Delivery Systems, Saint Paul, Minnesota, USA.
⁹ Schulich School of Medicine & Dentistry, The University of Western Ontario, London, Ontario, Canada.
¹⁰ Cellular Biology Section, Laboratory of Viral Diseases, NIAID, NIH, Bethesda, Maryland, USA.
¹¹ Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.
¹² Departments of Pathology, and Microbiology & Immunology, Institute for Immunity, Transplantation and Infection, Stanford University, Stanford, California, USA.

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.

Keywords: AIDS vaccine; AIDS/HIV; Adaptive immunity; Vaccines.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

AIDS Vaccines / administration & dosage
AIDS Vaccines / immunology*
Adjuvants, Immunologic / administration & dosage
Animals
Antibodies, Neutralizing / immunology
Antibodies, Viral / immunology*
CD8-Positive T-Lymphocytes / immunology
Disease Models, Animal
Female
Genetic Vectors / administration & dosage
Genetic Vectors / immunology
HIV Infections / blood
HIV Infections / immunology
HIV Infections / prevention & control*
HIV Infections / virology
HIV-1 / immunology
Heterocyclic Compounds, 3-Ring / administration & dosage
Heterocyclic Compounds, 3-Ring / immunology
Immunogenicity, Vaccine
Macaca mulatta
Mucous Membrane / immunology
Mucous Membrane / virology
Simian Acquired Immunodeficiency Syndrome / blood
Simian Acquired Immunodeficiency Syndrome / immunology
Simian Acquired Immunodeficiency Syndrome / prevention & control*
Simian Acquired Immunodeficiency Syndrome / virology
Simian Immunodeficiency Virus / immunology
Stearic Acids / administration & dosage
Stearic Acids / immunology
Treatment Outcome
Vaccination / methods
Vaccines, Synthetic / administration & dosage
Vaccines, Synthetic / immunology
Vagina / immunology
Vagina / virology
env Gene Products, Human Immunodeficiency Virus / administration & dosage
env Gene Products, Human Immunodeficiency Virus / genetics
env Gene Products, Human Immunodeficiency Virus / immunology*

Substances

AIDS Vaccines
Adjuvants, Immunologic
Antibodies, Neutralizing
Antibodies, Viral
Heterocyclic Compounds, 3-Ring
Stearic Acids
Vaccines, Synthetic
env Gene Products, Human Immunodeficiency Virus
gp140 envelope protein, Human immunodeficiency virus 1
MEDI9197

Abstract

Publication types

MeSH terms

Substances

Grants and funding