Defense-in-depth by mucosally administered anti-HIV dimeric IgA2 and systemic IgG1 mAbs: complete protection of rhesus monkeys from mucosal SHIV challenge

Vaccine
Anton SholukhRuth M Ruprecht

Abstract

Although IgA is the most abundantly produced immunoglobulin in humans, its role in preventing HIV-1 acquisition, which occurs mostly via mucosal routes, remains unclear. In our passive mucosal immunizations of rhesus macaques (RMs), the anti-HIV-1 neutralizing monoclonal antibody (nmAb) HGN194, given either as dimeric IgA1 (dIgA1) or dIgA2 intrarectally (i.r.), protected 83% or 17% of the RMs against i.r. simian-human immunodeficiency virus (SHIV) challenge, respectively. Data from the RV144 trial implied that vaccine-induced plasma IgA counteracted the protective effector mechanisms of IgG1 with the same epitope specificity. We thus hypothesized that mucosal dIgA2 might diminish the protection provided by IgG1 mAbs targeting the same epitope. To test our hypothesis, we administered HGN194 IgG1 intravenously (i.v.) either alone or combined with i.r. HGN194 dIgA2. We enrolled SHIV-exposed, persistently aviremic RMs protected by previously administered nmAbs; RM anti-human IgG responses were undetectable. However, low-level SIV Gag-specific proliferative T-cell responses were found. These animals resemble HIV-exposed, uninfected humans, in which local and systemic cellular immune responses have been observed. HGN194 IgG1 and dIgA...Continue Reading

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Citations

Oct 27, 2015·Immunological Reviews·Austin W BoeschMargaret E Ackerman
Oct 27, 2015·Immunological Reviews·Stian FossJan Terje Andersen
Nov 4, 2016·Nature Reviews. Drug Discovery·Guido FerrariGeorgia D Tomaras
Jan 31, 2017·Immunological Reviews·Amarendra PeguNancy L Haigwood
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Jan 17, 2019·Journal of Immunology Research·Ebony N Gary, Michele A Kutzler
Nov 28, 2019·Vaccines·Ruth M RuprechtRajesh Thippeshappa
Apr 25, 2018·Viruses·Lyvia FourcadeMichel Roger
Jul 31, 2018·AIDS Research and Human Retroviruses·Ester LopezAmy W Chung
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May 19, 2017·The Journal of Infectious Diseases·Guido FerrariBarton F Haynes
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Jul 9, 2021·Frontiers in Immunology·Erandi Velarde de la CruzAnna Aldovini

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