Antibody to the gp120 V1/V2 Loops and CD4(+) and CD8(+) T Cell Responses in Protection from SIVmac251 Vaginal Acquisition and Persistent Viremia

作者：Gordon Shari N; Doster Melvin N; Kines Rhonda C; Keele Brandon F; Brocca Cofano Egidio; Guan Yongjun; Pegu Poonam; Liyanage Namal P M; Vaccari Monica; Cuburu Nicolas; Buck Christopher B; Ferrari Guido; Montefiori David; Piatak Michael Jr; Lifson Jeffrey D; Xenophontos Anastasia M; Venzon David; Robert Guroff Marjorie; Graham Barney S; Lowy Douglas R; Schiller John T; Franchini Genoveffa^*

来源：The Journal of Immunology, 2014, 193(12): 6172-6183.

DOI：10.4049/jimmunol.1401504

The human papillomavirus pseudovirions (HPV-PsVs) approach is an effective gene-delivery system that can prime or boost an immune response in the vaginal tract of nonhuman primates and mice. Intravaginal vaccination with HPV-PsVs expressing SIV genes, combined with an i.m. gp120 protein injection, induced humoral and cellular SIV-specific responses in macaques. Priming systemic immune responses with i.m. immunization with ALVAC-SIV vaccines, followed by intravaginal HPV-PsV-SIV/gp120 boosting, expanded and/or recruited T cells in the female genital tract. Using a stringent repeated low-dose intravaginal challenge with the highly pathogenic SIVmac251, we show that although these regimens did not demonstrate significant protection from virus acquisition, they provided control of viremia in a number of animals. High-avidity Ab responses to the envelope gp120 V1/V2 region correlated with delayed SIVmac251 acquisition, whereas virus levels in mucosal tissues were inversely correlated with antienvelope CD4(+) T cell responses. CD8(+) T cell depletion in animals with controlled viremia caused an increase in tissue virus load in some animals, suggesting a role for CD8(+) T cells in virus control. This study highlights the importance of CD8(+) cells and antienvelope CD4(+) T cells in curtailing virus replication and antienvelope V1/V2 Abs in preventing SIVmac251 acquisition.

• 出版日期2014-12-15