Live simian immunodeficiency virus vaccine correlate of protection: Immune complex-inhibitory fc receptor interactions that reduce target cell availability

Anthony J. Smith, Stephen W. Wietgrefe, Liang Shang, Cavan S. Reilly, Peter J. Southern, Katherine E. Perkey, Lijie Duan, Heinz Kohler, Sybille Müller, James Robinson, John V. Carlis, Qingsheng Li, R. Paul Johnson, Ashley T. Haase

Research output: Contribution to journalArticle

27 Scopus citations

Abstract

Principles to guide design of an effective vaccine against HIV are greatly needed, particularly to protect women in the pandemic's epicenter in Africa. We have been seeking these principles by identifying correlates of the robust protection associated with SIVmac239Δnef vaccination in the SIV-rhesus macaque animal model of HIV-1 transmission to women. We identified one correlate of SIVmac239Δnef protection against vaginal challenge as a resident mucosal system for SIV-gp41 trimer Ab production and neonatal FcR-mediated concentration of these Abs on the path of virus entry to inhibit establishment of infected founder populations at the portal of entry. In this study, we identify blocking CD4+ T cell recruitment to thereby inhibit local expansion of infected founder populations as a second correlate of protection. Virus-specific immune complex interactions with the inhibitory FcγRIIb receptor in the epithelium lining the cervix initiate expression of genes that block recruitment of target cells to fuel local expansion. Immune complex-FcγRIIb receptor interactions at mucosal frontlines to dampen the innate immune response to vaginal challenge could be a potentially general mechanism for the mucosal immune system to sense and modulate the response to a previously encountered pathogen. Designing vaccines to provide protection without eliciting these transmission-promoting innate responses could contribute to developing an effective HIV-1 vaccine.

Original languageEnglish (US)
Pages (from-to)3126-3133
Number of pages8
JournalJournal of Immunology
Volume193
Issue number6
DOIs
StatePublished - Sep 15 2014

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Smith, A. J., Wietgrefe, S. W., Shang, L., Reilly, C. S., Southern, P. J., Perkey, K. E., Duan, L., Kohler, H., Müller, S., Robinson, J., Carlis, J. V., Li, Q., Johnson, R. P., & Haase, A. T. (2014). Live simian immunodeficiency virus vaccine correlate of protection: Immune complex-inhibitory fc receptor interactions that reduce target cell availability. Journal of Immunology, 193(6), 3126-3133. https://doi.org/10.4049/jimmunol.1400822