Induction of vaginal-resident HIV-specific CD8 T cells with mucosal prime-boost immunization

H. X. Tan, A. K. Wheatley, R. Esterbauer, S. Jegaskanda, J. J. Glass, D. Masopust, R. De Rose, S. J. Kent

Research output: Contribution to journalArticlepeer-review

36 Scopus citations


Tissue-resident memory (T RM) CD8 T cells survey a range of non-lymphoid mucosal tissues where they rapidly mediate clearance of viral infections at the entry portals. Vaccines that establish CD8 T RM cells in the cervicovaginal mucosa hold promise for effective immunity against sexually transmitted HIV. We demonstrate that HIV-specific CD8 T RM cells can be established in the murine vaginal mucosa using a combined intranasal and intravaginal mucosal immunization with recombinant influenza-HIV vectors. Using in situ tetramer immunofluorescence microscopy, we found that this mucosally administered prime-boost immunization also resulted in the durable seeding of CD8 T cells in the frontline vaginal epithelial compartment as opposed to the vaginal submucosa. Upon cognate antigen recognition within the vaginal mucosa, these HIV-specific CD8 T RM cells rapidly initiated a tissue-wide state of immunity. The activation of HIV-specific CD8 T RM cells resulted in the upregulation of endothelial vessel addressin expression and substantial recruitment of both adaptive and innate immune cells in the vaginal mucosa. These findings suggest that the epithelial localization of HIV-specific CD8 T RM cell populations and their capacity to rapidly activate both arms of the immune system could significantly augment frontline defenses against vaginal HIV infection.

Original languageEnglish (US)
Pages (from-to)994-1007
Number of pages14
JournalMucosal Immunology
Issue number3
StatePublished - May 1 2018

Bibliographical note

Funding Information:
This research was supported by the Australian Research Council and National Health and Medical Research Council, Australia.

Publisher Copyright:
© The Author(s) 2018.


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