Targeting the genital tract mucosa with a lipopeptide/recombinant adenovirus prime/boost vaccine induces potent and long-lasting CD8+ T cell immunity against herpes: Importance of MyD88

Xiuli Zhang, Xavier Dervillez, Aziz Alami Chentoufi, Tina Badakhshan, Ilham Bettahi, Lbachir BenMohamed*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

37 Citations (Scopus)

Abstract

Targeting of the mucosal immune system of the genital tract with subunit vaccines has failed to induce potent and durable local CD8+ T cell immunity, which is crucial for protection against many sexually transmitted viral pathogens, including HSV type 2 (HSV-2), which causes genital herpes. In this study, we aimed to investigate the potential of a novel lipopeptide/adenovirus type 5 (Lipo/rAdv5) prime/boost mucosal vaccine for induction of CD8+ T cell immunity to protect the female genital tract from herpes. The lipopeptide vaccine and the rAdv5 vaccine express the immunodominant HSV-2 CD8+ T cell epitope (gB498-505), and both were delivered intravaginally in the progesterone-induced B6 mouse model of genital herpes. Compared with mice immunized with the homologous lipopeptide/lipopeptide (Lipo/Lipo) vaccine, the Lipo/rAdv5 prime/boost immunized mice 1) developed potent and sustained HSV-specific CD8+ T cells, detected in both the genital tract draining nodes and in the vaginal mucosa; 2) had significantly lower virus titers; 3) had decreased overt signs of genital herpes disease; and 4) did not succumb to lethal infection (p < 0.005) after intravaginal HSV-2 challenge. Polyfunctional CD8+ T cells, producing IFN-γ, TNF-α, and IL-2 and exhibiting cytotoxic activity, were associated with protection ( p < 0.005). The protective CD8+ T cell response was significantly compromised in the absence of the adapter MyD88 ( p = 0.0001). Taken together, these findings indicate that targeting of the vaginal mucosa with a Lipo/rAdv5 prime/boost vaccine elicits a potent, MyD88-dependent, and long-lasting mucosal CD8+ T cell protective immunity against sexually transmitted herpes infection and disease.

Original languageEnglish
Pages (from-to)4496-4509
Number of pages14
JournalJournal of Immunology
Volume189
Issue number9
DOIs
Publication statusPublished - 1 Nov 2012
Externally publishedYes

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