Lymph node T cell responses predict the efficacy of live attenuated SIV vaccines.

Published

Journal Article

Live attenuated simian immunodeficiency virus (SIV) vaccines (LAVs) remain the most efficacious of all vaccines in nonhuman primate models of HIV and AIDS, yet the basis of their robust protection remains poorly understood. Here we show that the degree of LAV-mediated protection against intravenous wild-type SIVmac239 challenge strongly correlates with the magnitude and function of SIV-specific, effector-differentiated T cells in the lymph node but not with the responses of such T cells in the blood or with other cellular, humoral and innate immune parameters. We found that maintenance of protective T cell responses is associated with persistent LAV replication in the lymph node, which occurs almost exclusively in follicular helper T cells. Thus, effective LAVs maintain lymphoid tissue-based, effector-differentiated, SIV-specific T cells that intercept and suppress early wild-type SIV amplification and, if present in sufficient frequencies, can completely control and perhaps clear infection, an observation that provides a rationale for the development of safe, persistent vectors that can elicit and maintain such responses.

Full Text

Duke Authors

Cited Authors

  • Fukazawa, Y; Park, H; Cameron, MJ; Lefebvre, F; Lum, R; Coombes, N; Mahyari, E; Hagen, SI; Bae, JY; Reyes, MD; Swanson, T; Legasse, AW; Sylwester, A; Hansen, SG; Smith, AT; Stafova, P; Shoemaker, R; Li, Y; Oswald, K; Axthelm, MK; McDermott, A; Ferrari, G; Montefiori, DC; Edlefsen, PT; Piatak, M; Lifson, JD; Sékaly, RP; Picker, LJ

Published Date

  • November 2012

Published In

Volume / Issue

  • 18 / 11

Start / End Page

  • 1673 - 1681

PubMed ID

  • 22961108

Pubmed Central ID

  • 22961108

Electronic International Standard Serial Number (EISSN)

  • 1546-170X

Digital Object Identifier (DOI)

  • 10.1038/nm.2934

Language

  • eng

Conference Location

  • United States