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

Immunity
Matthias G PauthnerDennis R Burton

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 SHIVBG505 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.

Citations

Dec 19, 2018·Nature Reviews. Immunology·Dennis R Burton
Apr 12, 2019·Current Opinion in HIV and AIDS·Mar Naranjo-Gomez, Mireia Pelegrin
Feb 23, 2020·Nature Communications·Todd BradleyBarton F Haynes
Jun 28, 2020·Journal of Virology·John P Moore, P J Klasse
Sep 1, 2020·PLoS Pathogens·Christopher A CottrellMarit J van Gils
Sep 25, 2019·Vaccines·Sarah WilmschenJanine Kimpel
Nov 11, 2019·The Journal of Experimental Medicine·Ganesh E PhadGunilla B Karlsson Hedestam
Jul 3, 2020·Frontiers in Immunology·Diane G CarnathanMichela Locci
Jul 31, 2019·Proceedings of the National Academy of Sciences of the United States of America·Archana V BoopathyDarrell J Irvine
Feb 15, 2020·AIDS Research and Human Retroviruses·Alexander BontempoMark J Cayabyab
Apr 29, 2020·Annual Review of Immunology·Kathryn E StephensonDan H Barouch
Oct 6, 2020·Frontiers in Immunology·Alexander I Mosa
Apr 25, 2020·Frontiers in Bioengineering and Biotechnology·Phindile XimbaEdward P Rybicki
Dec 4, 2019·Expert Review of Vaccines·Iván Del Moral-Sánchez, Kwinten Sliepen
Nov 20, 2020·The Journal of Immunology : Official Journal of the American Association of Immunologists·Michael W GrunstDavid T Evans
Jul 1, 2020·Advanced Drug Delivery Reviews·Darrell J IrvineMurillo Silva
Apr 10, 2020·Cell Host & Microbe·P J KlasseJohn P Moore
Feb 5, 2021·The Journal of Immunology : Official Journal of the American Association of Immunologists·Ann J HessellMiroslaw K Gorny
Jun 30, 2019·Virology·Evonne WoodsonEric Hunter
Apr 17, 2021·NPJ Vaccines·Kelly E SeatonUNKNOWN NIAID HIV Vaccine Trials Network (HVTN) 076, 088, 086, 096, 097, 205 Study Teams

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Methods Mentioned

BETA
ELISA
transmission
dynamic light scattering
glycosylation
ELISAs
flow cytometry
FACS
PCR
size exclusion chromatography

Software Mentioned

FLEA
Prism
RELION
Leginon
Appion
PacBio
Graphpad Prism
FlowJo
Graphpad
DoG Picker

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