Vaccine-Induced Protection from Homologous Tier 2 SHIV Challenge in Nonhuman Primates Depends on Serum-Neutralizing Antibody Titers

Matthias G Pauthner; Joseph P Nkolola; Colin Havenar-Daughton; Ben Murrell; Samantha M Reiss; Raiza Bastidas; Jérémie Prévost; Rebecca Nedellec; Benjamin von Bredow; Peter Abbink; Christopher A Cottrell; Daniel W Kulp; Talar Tokatlian; Bartek Nogal; Matteo Bianchi; Hui Li; Jeong Hyun Lee; Salvatore T Butera; David T Evans; Lars Hangartner; Andrés Finzi; Ian A Wilson; Richard T Wyatt; Darrell J Irvine; William R Schief; Andrew B Ward; Rogier W Sanders; Shane Crotty; George M Shaw; Dan H Barouch; Dennis R Burton

doi:10.1016/j.immuni.2018.11.011

Vaccine-Induced Protection from Homologous Tier 2 SHIV Challenge in Nonhuman Primates Depends on Serum-Neutralizing Antibody Titers

Immunity. 2019 Jan 15;50(1):241-252.e6. doi: 10.1016/j.immuni.2018.11.011. Epub 2018 Dec 11.

Authors

Matthias G Pauthner¹, Joseph P Nkolola², Colin Havenar-Daughton³, Ben Murrell⁴, Samantha M Reiss³, Raiza Bastidas¹, Jérémie Prévost⁵, Rebecca Nedellec¹, Benjamin von Bredow⁶, Peter Abbink², Christopher A Cottrell⁷, Daniel W Kulp⁸, Talar Tokatlian⁹, Bartek Nogal⁷, Matteo Bianchi¹, Hui Li¹⁰, Jeong Hyun Lee³, Salvatore T Butera¹¹, David T Evans⁶, Lars Hangartner¹, Andrés Finzi¹², Ian A Wilson⁷, Richard T Wyatt¹, Darrell J Irvine¹³, William R Schief¹, Andrew B Ward⁷, Rogier W Sanders¹⁴, Shane Crotty¹⁵, George M Shaw¹⁶, Dan H Barouch¹⁷, Dennis R Burton¹⁸

Affiliations

¹ Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery (CHAVI-ID), The Scripps Research Institute, La Jolla, CA 92037, USA; IAVI Neutralizing Antibody Center and the Collaboration for AIDS Vaccine Discovery (CAVD), The Scripps Research Institute, La Jolla, CA 92037, USA.
² Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
³ Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery (CHAVI-ID), The Scripps Research Institute, La Jolla, CA 92037, USA; Division of Vaccine Discovery, La Jolla Institute for Immunology, La Jolla, CA 92037, USA.
⁴ Division of Infectious Diseases, Department of Medicine, University of California San Diego, La Jolla, CA 92037, USA.
⁵ Centre de Recherche du CHUM, Montreal, QC H2X 0A9, Canada; Department of Microbiology, Infectious Diseases and Immunology, Université de Montréal, Montreal, QC H2X 0A9, Canada.
⁶ Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, WI 53705, USA.
⁷ Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery (CHAVI-ID), The Scripps Research Institute, La Jolla, CA 92037, USA; IAVI Neutralizing Antibody Center and the Collaboration for AIDS Vaccine Discovery (CAVD), The Scripps Research Institute, La Jolla, CA 92037, USA; Department of Integrative Structural and Computational Biology and the Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
⁸ Vaccine and Immunotherapy Center, The Wistar Institute, Philadelphia, PA 19104, USA.
⁹ Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery (CHAVI-ID), The Scripps Research Institute, La Jolla, CA 92037, USA; Koch Institute for Integrative Cancer Research, MIT, Cambridge, MA 02139, USA.
¹⁰ Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
¹¹ Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery (CHAVI-ID), The Scripps Research Institute, La Jolla, CA 92037, USA.
¹² Centre de Recherche du CHUM, Montreal, QC H2X 0A9, Canada; Department of Microbiology, Infectious Diseases and Immunology, Université de Montréal, Montreal, QC H2X 0A9, Canada; Department of Microbiology and Immunology, McGill University, Montreal, QC H3A 2B4, Canada.
¹³ Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery (CHAVI-ID), The Scripps Research Institute, La Jolla, CA 92037, USA; Koch Institute for Integrative Cancer Research, MIT, Cambridge, MA 02139, USA; Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard University, Cambridge, MA 02139, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA; Departments of Biological Engineering and Materials Science & Engineering, MIT, Cambridge, MA 02139, USA.
¹⁴ Department of Medical Microbiology, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, the Netherlands; Department of Microbiology and Immunology, Weill Medical College of Cornell University, New York, NY 10065, USA.
¹⁵ Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery (CHAVI-ID), The Scripps Research Institute, La Jolla, CA 92037, USA; Division of Vaccine Discovery, La Jolla Institute for Immunology, La Jolla, CA 92037, USA; Division of Infectious Diseases, Department of Medicine, University of California San Diego, La Jolla, CA 92037, USA. Electronic address: [email protected].
¹⁶ Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address: [email protected].
¹⁷ Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA; Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard University, Cambridge, MA 02139, USA. Electronic address: [email protected].
¹⁸ Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA; Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery (CHAVI-ID), The Scripps Research Institute, La Jolla, CA 92037, USA; IAVI Neutralizing Antibody Center and the Collaboration for AIDS Vaccine Discovery (CAVD), The Scripps Research Institute, La Jolla, CA 92037, USA; Ragon Institute of Massachusetts General Hospital, Massachusetts Institute of Technology, and Harvard University, Cambridge, MA 02139, USA. Electronic address: [email protected].

Abstract

Passive administration of HIV neutralizing antibodies (nAbs) can protect macaques from hard-to-neutralize (tier 2) chimeric simian-human immunodeficiency virus (SHIV) challenge. However, conditions for nAb-mediated protection after vaccination have not been established. Here, we selected groups of 6 rhesus macaques with either high or low serum nAb titers from a total of 78 animals immunized with recombinant native-like (SOSIP) Env trimers. Repeat intrarectal challenge with homologous tier 2 SHIV_BG505 led to rapid infection in unimmunized and low-titer animals. High-titer animals, however, demonstrated protection that was gradually lost as nAb titers waned over time. An autologous serum ID₅₀ nAb titer of ∼1:500 afforded more than 90% protection from medium-dose SHIV infection. In contrast, antibody-dependent cellular cytotoxicity and T cell activity did not correlate with protection. Therefore, Env protein-based vaccination strategies can protect against hard-to-neutralize SHIV challenge in rhesus macaques by inducing tier 2 nAbs, provided appropriate neutralizing titers can be reached and maintained.

Keywords: ADCC; BG505; HIV vaccine; correlates of protection; neutralizing antibodies; non-human primates; tier 2 protection; vaccination.

Publication types

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

MeSH terms

AIDS Vaccines / immunology*
Animals
Antibodies, Neutralizing / immunology
HIV / physiology*
HIV Antibodies / immunology*
HIV Infections / immunology*
Humans
Macaca mulatta
Simian Acquired Immunodeficiency Syndrome / immunology*
Simian Immunodeficiency Virus / physiology*
Vaccination
env Gene Products, Human Immunodeficiency Virus / immunology*

Substances

AIDS Vaccines
Antibodies, Neutralizing
HIV Antibodies
env Gene Products, Human Immunodeficiency Virus

Abstract

Publication types

MeSH terms

Substances

Grants and funding