Anti-HIV IgM protects against mucosal SHIV transmission

AIDS
Siqi GongR M Ruprecht

Abstract

Worldwide, most new HIV infections occur through mucosal exposure. Immunoglobulin M (IgM) is the first antibody class generated in response to infectious agents; IgM is present in the systemic circulation and in mucosal fluids as secretory IgM. We sought to investigate for the first time the role of IgM in preventing AIDS virus acquisition in vivo. Recombinant polymeric monoclonal IgM was generated from the neutralizing monoclonal IgG1 antibody 33C6-IgG1, tested in vitro, and given by passive intrarectal immunization to rhesus macaques 30 min before intrarectal challenge with simian-human immunodeficiency virus (SHIV) that carries an HIV-1 envelope gene. In vitro, 33C6-IgM captured virions more efficiently and neutralized the challenge SHIV with a 50% inhibitory molar concentration (IC50) that was 1 log lower than that for 33C6-IgG1. The IgM form also exhibited significantly higher affinity and avidity compared with 33C6-IgG1. After intrarectal administration, 33C6-IgM prevented viremia in four out of six rhesus macaques after high-dose intrarectal SHIV challenge. Five out of six rhesus macaques given 33C6-IgG1 were protected at a five times higher molar concentration compared with the IgM form; all untreated controls became hi...Continue Reading

References

Dec 10, 2002·The Journal of Immunology : Official Journal of the American Association of Immunologists·Nicole Baker, Michael R Ehrenstein
Mar 5, 2004·Proceedings of the National Academy of Sciences of the United States of America·Ming ZhangMichael C Carroll
Nov 3, 2009·Cell·Lakshmi SrinivasanKlaus Rajewsky
Dec 17, 2009·Cell Research·Jason R Dunkelberger, Wen-Chao Song
Jan 6, 2010·Current Opinion in HIV and AIDS·Georgia D Tomaras, Barton F Haynes
Dec 15, 2010·The Journal of Immunology : Official Journal of the American Association of Immunologists·Rachael RacineGary M Winslow
Jun 14, 2013·Journal of Virology·Corin L DorfmeierJames P McGettigan
Jun 28, 2013·The Journal of Immunology : Official Journal of the American Association of Immunologists·Jennifer L YatesGary M Winslow
May 20, 2015·Nature Immunology·Dennis R Burton, John R Mascola
Apr 20, 2017·Current Opinion in HIV and AIDS·Ruth M Ruprecht, Samir K Lakhashe

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Citations

May 15, 2019·Current Opinion in HIV and AIDS·Boris Julg, Dan H Barouch
Jun 30, 2018·AIDS·Barbara Schmidt
Nov 28, 2019·Vaccines·Ruth M RuprechtRajesh Thippeshappa
Aug 28, 2020·Frontiers in Immunology·Siqi Gong, Ruth M Ruprecht
Feb 8, 2019·Frontiers in Immunology·Thevani PillayDerseree Archary
Oct 18, 2020·Antibodies·Bruce A KeytMarvin S Peterson
Feb 16, 2021·The Journal of Infectious Diseases·Evan RossignolBoris Julg
Apr 17, 2021·Seminars in Immunology·Boris Julg, Dan Barouch

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Methods Mentioned

BETA
surface plasmon resonance
Dynamic light scattering

Software Mentioned

GraphPad
GraphPad Prism

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