Antibody to the gp120 V1/V2 loops and CD4+ and CD8+ T cell responses in protection from SIVmac251 vaginal acquisition and persistent viremia.

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Gordon, SN; Doster, MN; Kines, RC; Keele, BF; Brocca-Cofano, E; Guan, Y; Pegu, P; Liyanage, NPM; Vaccari, M; Cuburu, N; Buck, CB; Ferrari, G; Montefiori, D; Piatak, M; Lifson, JD; Xenophontos, AM; Venzon, D; Robert-Guroff, M; Graham, BS; Lowy, DR; Schiller, JT; Franchini, G

Published Date

  • December 2014

Published In

Volume / Issue

  • 193 / 12

Start / End Page

  • 6172 - 6183

PubMed ID

  • 25398324

Pubmed Central ID

  • 25398324

Electronic International Standard Serial Number (EISSN)

  • 1550-6606

International Standard Serial Number (ISSN)

  • 0022-1767

Digital Object Identifier (DOI)

  • 10.4049/jimmunol.1401504

Language

  • eng