@article{d54510d9670b4c5fb7eb96dbe39e1ba0,
title = "Lymph node T cell responses predict the efficacy of live attenuated SIV vaccines",
abstract = "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.",
author = "Yoshinori Fukazawa and Haesun Park and Cameron, {Mark J.} and Francois Lefebvre and Richard Lum and Noel Coombes and Eisa Mahyari and Hagen, {Shoko I.} and Bae, {Jin Young} and Reyes, {Marcelo Delos} and Tonya Swanson and Legasse, {Alfred W.} and Andrew Sylwester and Hansen, {Scott G.} and Smith, {Andrew T.} and Petra Stafova and Rebecca Shoemaker and Yuan Li and Kelli Oswald and Axthelm, {Michael K.} and Adrian McDermott and Guido Ferrari and Montefiori, {David C.} and Edlefsen, {Paul T.} and Michael Piatak and Lifson, {Jeffrey D.} and S{\'e}kaly, {Rafick P.} and Picker, {Louis J.}",
note = "Funding Information: grant R37 AI054292 (L.J.P.), contract HHSN272200900037C and the Center for HIV-AIDS Vaccine Immunology (CHAVI) program), the NIH Office of Research Infrastructure Programs (P51 OD 011092) and the National Cancer Institute (contract HHSN261200800001E). The authors acknowledge R. Desrosiers (Harvard University) for providing SIVmac239∆nef and SIVmac239∆3; P. Johnson and T. Lui (University of Pennsylvania) for SIVsmE543∆nef; C. Miller (University of California, Davis) for SHIV89.6 and wild-type SIVmac239; D. Evans (Harvard University) for a single-cycle SIVmac239; N. Letvin for TRIM5 allele typing; and R. Wiseman and D. Watkins for MHC typing. We thank N. Winstone, A. Leon, J. Clock, A. Nogueron, L. Pan, M. Cartwright, A. Filali and P. Wilkinson for technical assistance and J. McElrath, S. Self, W. Koff, A. Okoye, J. Schmitz and J. Ahler for helpful discussion and advice. Funding Information: This work was supported by the Bill and Melinda Gates Foundation (grant #41185), the International AIDS Vaccine Initiative (IAVI), the National Institute of Allergy and Infectious Diseases (including the US National Institutes of Health (NIH)",
year = "2012",
month = nov,
doi = "10.1038/nm.2934",
language = "English (US)",
volume = "18",
pages = "1673--1681",
journal = "Nature medicine",
issn = "1078-8956",
publisher = "Nature Publishing Group",
number = "11",
}