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

Matthias G PauthnerDennis R Burton


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.


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

dynamic light scattering
flow cytometry
size exclusion chromatography

Software Mentioned

Graphpad Prism
DoG Picker

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