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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
immunology and microbiology
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
Journal of Immunology, Volume 189, No. 9, Year 2012
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Description
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. Copyright © 2012 by The American Association of Immunologists, Inc.
Authors & Co-Authors
Zhang, Xiuli
United States, Irvine
University of California, Irvine
United States, St. Louis
Washington University School of Medicine in St. Louis
Dervillez, Xavier
United States, Irvine
University of California, Irvine
Chentoufi, Aziz Alami
United States, Irvine
University of California, Irvine
Saudi Arabia, Riyadh
King Fahad Medical City
Badakhshan, Tina
United States, Irvine
University of California, Irvine
Bettahi, Ilham
United States, Irvine
University of California, Irvine
United States, Detroit
Kresge Eye Institute
BenMohamed, Lbachir
United States, Irvine
University of California, Irvine
United States, Irvine
Uci School of Medicine
Statistics
Citations: 49
Authors: 6
Affiliations: 5
Identifiers
Doi:
10.4049/jimmunol.1201121
ISSN:
00221767
e-ISSN:
15506606
Research Areas
Sexual And Reproductive Health
Participants Gender
Female