Mucosal humoral immune response to SIVmac239Δnef vaccination and vaginal challenge

Ming Zeng, Anthony J. Smith, Liang Shang, Stephen W. Wietgrefe, James E. Voss, John V. Carlis, Qingsheng Li, Michael Piatak, Jeffrey D. Lifson, R. Paul Johnson, Ashley T. Haase

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

Live attenuated vaccines such as SIV with a deleted nef gene have provided the most robust protection against subsequent vaginal challenge with wild-type (WT) SIV in the SIV-rhesus macaque model of HIV-1 transmission to women. Hence, identifying correlates of this protection could enable design of an effective HIV-1 vaccine. One such prechallenge correlate of protection from vaginal challenge has recently been identified as a system with three components: 1) IgG Abs reacting with the viral envelope glycoprotein trimeric gp41; 2) produced by plasma cells in the submucosa and ectopic tertiary lymphoid follicles in the ectocervix and vagina; and 3) concentrated on the path of virus entry by the neonatal FcR in the overlying epithelium. We now examine the mucosal production of the Ab component of this system after vaginal challenge. We show that vaginal challenge immediately elicits striking increases in plasma cells not only in the female reproductive tract but also at other mucosal sites, and that these increases correlate with low but persistent replication at mucosal sites. We describe vaginal ectopic follicles that are structurally and functionally organized similar to follicles in secondary lymphoid organs, and we provide inferential evidence for a key role of the female reproductive tract epithelium in facilitating Ab production, affinity maturation, and class switch recombination. Vaccination thus accesses an epithelial-immune system axis in the female reproductive tract to respond to exposure to mucosal pathogens. Designing strategies to mimic this system could advance development of an effective HIV-1 vaccine.

Original languageEnglish (US)
Pages (from-to)2809-2818
Number of pages10
JournalJournal of Immunology
Volume196
Issue number6
DOIs
StatePublished - Mar 15 2016

Fingerprint Dive into the research topics of 'Mucosal humoral immune response to SIVmac239Δnef vaccination and vaginal challenge'. Together they form a unique fingerprint.

  • Cite this

    Zeng, M., Smith, A. J., Shang, L., Wietgrefe, S. W., Voss, J. E., Carlis, J. V., Li, Q., Piatak, M., Lifson, J. D., Johnson, R. P., & Haase, A. T. (2016). Mucosal humoral immune response to SIVmac239Δnef vaccination and vaginal challenge. Journal of Immunology, 196(6), 2809-2818. https://doi.org/10.4049/jimmunol.1500156