Anti-HIV IgM protects against mucosal SHIV transmission

Siqi Gong, Khamis Tomusange, Viraj Kulkarni, Opeyemi S. Adeniji, Samir K. Lakhashe, Dinesh Hariraju, Amanda Strickland, Elizabeth Plake, Patrice A. Frost, Sarah J. Ratcliffe, Liping Wang, Eileen M. Lafer, Ruth M. Ruprecht

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

Objective: 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. Design: 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. Results: In vitro, 33C6-IgM captured virions more efficiently and neutralized the challenge SHIV with a 50% inhibitory molar concentration (IC 50) 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 highly viremic. Rhesus macaques passively immunized with 33C6-IgM with breakthrough infection had notably early development of autologous neutralizing antibody responses. Conclusion: Our primate model data provide the first proof-of-concept that mucosal IgM can prevent mucosal HIV transmission and have implications for HIV prevention and vaccine development.

Original languageEnglish (US)
Pages (from-to)F5-F13
JournalAIDS
Volume32
Issue number11
DOIs
StatePublished - Jul 17 2018

Keywords

  • HIV neutralization
  • IgM
  • R5 SHIV
  • mucosal transmission
  • virion capture

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

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