Vaccine-Associated Maintenance of Epithelial Integrity Correlated With Protection Against Virus Entry.
J Infect Dis
; 218(8): 1272-1283, 2018 09 08.
Article
in En
| MEDLINE
| ID: mdl-29401315
ABSTRACT
To identify the mechanisms by which human immunodeficiency virus type 1 (HIV-1) might penetrate the epithelial barrier during sexual transmission to women and the mechanisms of vaccine-associated protection against entry, we characterized early epithelial responses to vaginal inoculation of simian immunodeficiency virus strain mac251 (SIVmac251) in naive or SIVmac239Δnef-vaccinated rhesus macaques. Vaginal inoculation induced an early stress response in the cervicovaginal epithelium, which was associated with impaired epithelial integrity, damaged barrier function, and virus and bacterial translocation. In vaccinated animals, early stress responses were suppressed, and the maintenance of epithelial barrier integrity correlated with prevention of virus entry. These vaccine-protective effects were associated with a previously described mucosal system for locally producing and concentrating trimeric gp41 antibodies at the mucosal interface and with formation of SIV-specific immune complexes that block the stress responses via binding to the epithelial receptor FCGR2B and subsequent inhibitory signaling. Thus, blocking virus entry may be one protective mechanism by which locally concentrated non-neutralizing Ab might prevent HIV sexual transmission to women.
Full text:
1
Database:
MEDLINE
Main subject:
Viral Vaccines
/
Simian Acquired Immunodeficiency Syndrome
/
Simian Immunodeficiency Virus
/
Virus Internalization
Type of study:
Risk_factors_studies
Limits:
Animals
Language:
En
Journal:
J Infect Dis
Year:
2018
Type:
Article