Vaccine-associated maintenance of epithelial integrity correlated with protection against virus entry

Liang Shang, A. J. Smith, Lijie Duan, K. E. Perkey, Stephen W Wietgrefe, M. Zupancic, Peter Southern, R. P. Johnson, John V Carlis, Ashley T Haase

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)1272-1283
Number of pages12
JournalJournal of Infectious Diseases
Volume218
Issue number8
DOIs
StatePublished - Sep 8 2018

Fingerprint

Virus Internalization
Vaccines
Maintenance
Bacterial Translocation
Simian Immunodeficiency Virus
Antigen-Antibody Complex
Macaca mulatta
HIV-1
Epithelium
HIV
Viruses
Antibodies

Keywords

  • Epithelium
  • Epithelium integrity
  • Female reproductive tract
  • SIV
  • SIVΔnef

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

Cite this

Vaccine-associated maintenance of epithelial integrity correlated with protection against virus entry. / Shang, Liang; Smith, A. J.; Duan, Lijie; Perkey, K. E.; Wietgrefe, Stephen W; Zupancic, M.; Southern, Peter; Johnson, R. P.; Carlis, John V; Haase, Ashley T.

In: Journal of Infectious Diseases, Vol. 218, No. 8, 08.09.2018, p. 1272-1283.

Research output: Contribution to journalArticle

Shang, Liang ; Smith, A. J. ; Duan, Lijie ; Perkey, K. E. ; Wietgrefe, Stephen W ; Zupancic, M. ; Southern, Peter ; Johnson, R. P. ; Carlis, John V ; Haase, Ashley T. / Vaccine-associated maintenance of epithelial integrity correlated with protection against virus entry. In: Journal of Infectious Diseases. 2018 ; Vol. 218, No. 8. pp. 1272-1283.
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