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

Yoshinori Fukazawa, Haesun Park, Mark J. Cameron, Francois Lefebvre, Richard Lum, Noel Coombes, Eisa Mahyari, Shoko I. Hagen, Jin Young Bae, Marcelo Delos Reyes, Tonya Swanson, Alfred W. Legasse, Andrew Sylwester, Scott Hansen, Andrew T. Smith, Petra Stafova, Rebecca Shoemaker, Yuan Li, Kelli Oswald, Michael AxthelmAdrian McDermott, Guido Ferrari, David C. Montefiori, Paul T. Edlefsen, Michael Piatak, Jeffrey D. Lifson, Rafick P. Sékaly, Louis Picker

Research output: Contribution to journalArticle

101 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1673-1681
Number of pages9
JournalNature Medicine
Volume18
Issue number11
DOIs
StatePublished - Nov 2012

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Simian Immunodeficiency Virus
T-cells
Viruses
Vaccines
Lymph Nodes
T-Lymphocytes
Lymphoid Tissue
Helper-Inducer T-Lymphocytes
Primates
Acquired Immunodeficiency Syndrome
Maintenance
Observation
HIV
Amplification
Blood
Tissue
Infection

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Lymph node T cell responses predict the efficacy of live attenuated SIV vaccines. / Fukazawa, Yoshinori; Park, Haesun; Cameron, Mark J.; Lefebvre, Francois; Lum, Richard; Coombes, Noel; Mahyari, Eisa; Hagen, Shoko I.; Bae, Jin Young; Reyes, Marcelo Delos; Swanson, Tonya; Legasse, Alfred W.; Sylwester, Andrew; Hansen, Scott; Smith, Andrew T.; Stafova, Petra; Shoemaker, Rebecca; Li, Yuan; Oswald, Kelli; Axthelm, Michael; McDermott, Adrian; Ferrari, Guido; Montefiori, David C.; Edlefsen, Paul T.; Piatak, Michael; Lifson, Jeffrey D.; Sékaly, Rafick P.; Picker, Louis.

In: Nature Medicine, Vol. 18, No. 11, 11.2012, p. 1673-1681.

Research output: Contribution to journalArticle

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, S, Smith, AT, Stafova, P, Shoemaker, R, Li, Y, Oswald, K, Axthelm, M, McDermott, A, Ferrari, G, Montefiori, DC, Edlefsen, PT, Piatak, M, Lifson, JD, Sékaly, RP & Picker, L 2012, 'Lymph node T cell responses predict the efficacy of live attenuated SIV vaccines', Nature Medicine, vol. 18, no. 11, pp. 1673-1681. https://doi.org/10.1038/nm.2934
Fukazawa Y, Park H, Cameron MJ, Lefebvre F, Lum R, Coombes N et al. Lymph node T cell responses predict the efficacy of live attenuated SIV vaccines. Nature Medicine. 2012 Nov;18(11):1673-1681. https://doi.org/10.1038/nm.2934
Fukazawa, Yoshinori ; Park, Haesun ; Cameron, Mark J. ; Lefebvre, Francois ; Lum, Richard ; Coombes, Noel ; Mahyari, Eisa ; Hagen, Shoko I. ; Bae, Jin Young ; Reyes, Marcelo Delos ; Swanson, Tonya ; Legasse, Alfred W. ; Sylwester, Andrew ; Hansen, Scott ; Smith, Andrew T. ; Stafova, Petra ; Shoemaker, Rebecca ; Li, Yuan ; Oswald, Kelli ; Axthelm, Michael ; McDermott, Adrian ; Ferrari, Guido ; Montefiori, David C. ; Edlefsen, Paul T. ; Piatak, Michael ; Lifson, Jeffrey D. ; Sékaly, Rafick P. ; Picker, Louis. / Lymph node T cell responses predict the efficacy of live attenuated SIV vaccines. In: Nature Medicine. 2012 ; Vol. 18, No. 11. pp. 1673-1681.
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