UMMS Affiliation

Nonhuman Primate Reagent Resource, MassBiologics

Publication Date

2021-03-16

Document Type

Article

Disciplines

Immunology of Infectious Disease | Immunoprophylaxis and Therapy | Immunotherapy | Infectious Disease | Virus Diseases | Viruses

Abstract

The antiviral properties of broadly neutralizing antibodies against HIV are well-documented but no vaccine is currently able to elicit protective titers of these responses in primates. While current vaccine modalities can readily induce non-neutralizing antibodies against simian immunodeficiency virus (SIV) and HIV, the ability of these responses to restrict lentivirus transmission and replication remains controversial. Here, we investigated the antiviral properties of non-neutralizing antibodies in a group of Indian rhesus macaques (RMs) that were vaccinated with vif, rev, tat, nef, and env, as part of a previous study conducted by our group. These animals manifested rapid and durable control of viral replication to below detection limits shortly after SIVmac239 infection. Although these animals had no serological neutralizing activity against SIVmac239 prior to infection, their pre-challenge titers of Env-binding antibodies correlated with control of viral replication. To assess the contribution of anti-Env humoral immune responses to virologic control in two of these animals, we transiently depleted their circulating antibodies via extracorporeal plasma immunoadsorption and inhibition of IgG recycling through antibody-mediated blockade of the neonatal Fc receptor. These procedures reduced Ig serum concentrations by up to 80% and temporarily induced SIVmac239 replication in these animals. Next, we transferred purified total Ig from the rapid controllers into six vaccinated RMs one day before intrarectal challenge with SIVmac239. Although recipients of the hyperimmune anti-SIV Ig fraction were not protected from infection, their peak and chronic phase viral loads were significantly lower than those in concurrent unvaccinated control animals. Together, our results suggest that non-neutralizing Abs may play a role in the suppression of SIVmac239 viremia.

Keywords

SIV, adoptive transfer, anti-FcRn Ab, antibody depletion, immunoadsorption, non-neutralizing antibodies, rhesus macaques (Macaca mulatta)

Rights and Permissions

Copyright © 2021 Pedreño-Lopez, Rosen, Flores, Gorman, Voigt, Ricciardi, Crosno, Weisgrau, Parks, Lifson, Alter, Rakasz, Magnani, Martins and Watkins. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

DOI of Published Version

10.3389/fimmu.2021.657424

Source

Pedreño-Lopez N, Rosen BC, Flores WJ, Gorman MJ, Voigt TB, Ricciardi MJ, Crosno K, Weisgrau KL, Parks CL, Lifson JD, Alter G, Rakasz EG, Magnani DM, Martins MA, Watkins DI. Non-neutralizing Antibodies May Contribute to Suppression of SIVmac239 Viremia in Indian Rhesus Macaques. Front Immunol. 2021 Mar 16;12:657424. doi: 10.3389/fimmu.2021.657424. PMID: 33796119; PMCID: PMC8008062. Link to article on publisher's site

Journal/Book/Conference Title

Frontiers in immunology

Related Resources

Link to Article in PubMed

PubMed ID

33796119

Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

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