Vaccine-Associated Maintenance of Epithelial Integrity Correlated With Protection Against Virus Entry

Area of Science:

• Immunology
• Virology
• Microbiology

Background:

• Sexual transmission of Human Immunodeficiency Virus type 1 (HIV-1) to women involves breaching the cervicovaginal epithelial barrier.
• Understanding vaccine-induced protection against HIV-1 entry is crucial for developing effective prevention strategies.

Purpose of the Study:

• To investigate early epithelial responses to vaginal simian immunodeficiency virus (SIV) inoculation in naive and vaccinated macaques.
• To elucidate mechanisms of vaccine-associated protection against SIV/HIV-1 entry.

Main Methods:

• Characterization of early cervicovaginal epithelial responses following vaginal SIVmac251 inoculation in naive and SIVmac239Δnef-vaccinated rhesus macaques.
• Assessment of epithelial integrity, barrier function, and virus/bacterial translocation.
• Analysis of mucosal antibody systems, immune complexes, and epithelial receptor interactions (FCGR2B).

Main Results:

• Vaginal SIV inoculation induced epithelial stress responses, impaired barrier function, and translocation of virus and bacteria.
• Vaccinated animals showed suppressed stress responses and maintained epithelial barrier integrity, correlating with prevention of virus entry.
• Vaccine protection involved local concentration of trimeric gp41 antibodies and formation of SIV-specific immune complexes that inhibited epithelial stress responses via FCGR2B.

Conclusions:

• Blocking virus entry by locally concentrated, non-neutralizing antibodies is a potential mechanism for preventing HIV sexual transmission.
• Maintaining epithelial barrier integrity and suppressing stress responses are key vaccine-protective effects against SIV/HIV-1 mucosal transmission.