Live simian immunodeficiency virus vaccine correlate of protection: Local antibody production and concentration on the path of virus entry

Qingsheng Li, Ming Zeng, Lijie Duan, James E. Voss, Anthony J. Smith, Stefan Pambuccian, Liang Shang, Stephen Wietgrefe, Peter J. Southern, Cavan S. Reilly, Pamela J. Skinner, Mary L. Zupancic, John V. Carlis, Michael Piatak, Diane Waterman, R. Keith Reeves, Katherine Masek-Hammerman, Cynthia A. Derdeyn, Michael D. Alpert, David T. EvansHeinz Kohler, Sybille Müller, James Robinson, Jeffrey D. Lifson, Dennis R. Burton, R. Paul Johnson, Ashley T. Haase

Research output: Contribution to journalArticle

47 Scopus citations

Abstract

We sought design principles for a vaccine to prevent HIV transmission to women by identifying correlates of protection conferred by a highly effective live attenuated SIV vaccine in the rhesus macaque animal model. We show that SIVmac239Δnef vaccination recruits plasma cells and induces ectopic lymphoid follicle formation beneath the mucosal epithelium in the rhesus macaque female reproductive tract. The plasma cells and ectopic follicles produce IgG Abs reactive with viral envelope glycoprotein gp41 trimers, and these Abs are concentrated on the path of virus entry by the neonatal FcR in cervical reserve epithelium and in vaginal epithelium. This local Ab production and delivery system correlated spatially and temporally with the maturation of local protection against high-dose pathogenic SIV vaginal challenge. Thus, designing vaccines to elicit production and concentration of Abs at mucosal frontlines could aid in the development of an effective vaccine to protect women against HIV-1.

Original languageEnglish (US)
Pages (from-to)3113-3125
Number of pages13
JournalJournal of Immunology
Volume193
Issue number6
DOIs
StatePublished - Sep 15 2014

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Li, Q., Zeng, M., Duan, L., Voss, J. E., Smith, A. J., Pambuccian, S., Shang, L., Wietgrefe, S., Southern, P. J., Reilly, C. S., Skinner, P. J., Zupancic, M. L., Carlis, J. V., Piatak, M., Waterman, D., Reeves, R. K., Masek-Hammerman, K., Derdeyn, C. A., Alpert, M. D., ... Haase, A. T. (2014). Live simian immunodeficiency virus vaccine correlate of protection: Local antibody production and concentration on the path of virus entry. Journal of Immunology, 193(6), 3113-3125. https://doi.org/10.4049/jimmunol.1400820