Non-neutralizing Antibodies May Contribute to Suppression of SIVmac239 Viremia in Indian Rhesus Macaques
Authors
Pedreno-Lopez, NuriaRosen, Brandon C.
Flores, Walter J.
Gorman, Matthew J.
Voigt, Thomas B.
Ricciardi, Michael J.
Crosno, Kristin
Weisgrau, Kim L.
Parks, Christopher L.
Lifson, Jeffrey D.
Alter, Galit
Rakasz, Eva G.
Magnani, Diogo
Martins, Mauricio A.
Watkins, David I.
UMass Chan Affiliations
Nonhuman Primate Reagent Resource, MassBiologicsDocument Type
Journal ArticlePublication Date
2021-03-16Keywords
SIVadoptive transfer
anti-FcRn Ab
antibody depletion
immunoadsorption
non-neutralizing antibodies
rhesus macaques (Macaca mulatta)
Immunology of Infectious Disease
Immunoprophylaxis and Therapy
Immunotherapy
Infectious Disease
Virus Diseases
Viruses
Metadata
Show full item recordAbstract
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.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
DOI
10.3389/fimmu.2021.657424Permanent Link to this Item
http://hdl.handle.net/20.500.14038/41834PubMed ID
33796119Related Resources
Rights
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.Distribution License
http://creativecommons.org/licenses/by/4.0/ae974a485f413a2113503eed53cd6c53
10.3389/fimmu.2021.657424
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Except where otherwise noted, this item's license is described as 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.