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.

• Authors: Yoshinori Fukazawa, Haesun Park, Mark J Cameron, Francois Lefebvre, Richard Lum, Noel Coombes, Eisa Mahyari, Shoko I Hagen, Jin Young Bae, Marcelo Delos Reyes 3rd, Tonya Swanson, Alfred W Legasse, Andrew Sylwester, Scott G Hansen, Andrew T Smith, Petra Stafova, Rebecca Shoemaker, Yuan Li, Kelli Oswald, Michael K Axthelm, Adrian McDermott, Guido Ferrari, David C Montefiori, Paul T Edlefsen, Michael Piatak Jr, Jeffrey D Lifson, Rafick P Sékaly, Louis J Picker
• Journal: Nature medicine (Nat Med) Vol. 18 Issue 11 Pg. 1673-81 (Nov 2012) ISSN: 1546-170X [Electronic] United States
• PMID: 22961108 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• SAIDS Vaccines
• Vaccines, Attenuated

Topics

• Animals
• CD8-Positive T-Lymphocytes (cytology, immunology)
• Humans
• Immunity, Innate
• Leukocytes, Mononuclear (cytology, immunology)
• Lymph Nodes (cytology, immunology)
• Macaca mulatta (immunology, virology)
• Male
• SAIDS Vaccines (administration & dosage, immunology)
• Simian Acquired Immunodeficiency Syndrome (immunology, virology)
• Simian Immunodeficiency Virus (immunology, pathogenicity)
• Tissue Distribution
• Vaccines, Attenuated (immunology)
• Virus Replication (genetics)