Anti-HIV IgM protects against mucosal SHIV transmission

Area of Science:

• Immunology
• Virology
• Infectious Diseases

Background:

• Most new HIV infections occur via mucosal exposure.
• Immunoglobulin M (IgM) is the first antibody produced during infection and is found in mucosal fluids.
• The role of IgM in preventing HIV acquisition has not been previously investigated in vivo.

Purpose of the Study:

• To investigate the role of Immunoglobulin M (IgM) in preventing Simian-human immunodeficiency virus (SHIV) acquisition in vivo.
• To compare the efficacy of IgM and IgG1 in passive mucosal immunization against HIV.

Main Methods:

• Recombinant polymeric monoclonal IgM was generated from a neutralizing monoclonal IgG1 antibody (33C6-IgG1).
• The efficacy of 33C6-IgM was tested in vitro and via passive intrarectal immunization in rhesus macaques.
• Macaques were challenged intrarectally with SHIV, and protection was assessed by viremia levels.

Main Results:

• In vitro, 33C6-IgM demonstrated more efficient viral capture and higher neutralization potency than 33C6-IgG1.
• Passive intrarectal immunization with 33C6-IgM protected 4 out of 6 macaques from SHIV viremia.
• A higher concentration of 33C6-IgG1 protected 5 out of 6 macaques, while controls showed high viremia.

Conclusions:

• This study provides the first proof-of-concept that mucosal IgM can prevent mucosal HIV transmission in a primate model.
• These findings have significant implications for HIV prevention strategies and vaccine development.
• Mucosal IgM represents a potential new avenue for developing effective HIV prevention methods.