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

Fukazawa Y, Park H, Cameron MJ, Lefebvre F, Lum R, Coombes N, et al.

Nature Medicine 2012, 18(11): 1673-1681.

Speaker: Chin-Yu Chen (陳謦伃)                                          Time: 13:10~14:00, May 1, 2013

Commentator: Shainn-Wei Wang, Ph.D. (王憲威老師)     Place: Room 601

Abstract:

Live attenuated simian immunodeficiency virus (SIV) vaccines (LAVs) have been known to be capable of preventing the acquisition of viral infection after challenge with highly pathogenic SIV and remain the most efficacious vaccines in nonhuman primate models of HIV and AIDS ¹. However, the mechanisms of LAV-mediated protection have not been clear ². In this study, the authors vaccinate groups of macaques with different LAVs that vary in their level of attenuation and their degree of amino acid sequence homology with the wild-type SIVmac239 challenge virus. Results show that the degree of LAV-mediated protection against intravenous wild-type SIVmac239 challenge strongly correlates with the magnitude and function of SIV-specific T cells in the lymph node, but not in the blood. In addition, the 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. Notably, the germinal centers of lymph nodes seem to provide a refuge for replicating LAV. The levels of LAV replication in germinal centers correlate with the numbers of protective T cells in the lymph node. These results reveal a novel sanctuary from which replicating LAV can stimulate protective T cell responses to its host.

References:

1.      Daniel, M.D., Kirchhoff, F., Czajak, S.C., Sehgal, P.K., Desrosiers, R.C. Protective effects of live attenuated SIV vaccine with a deletion in the nef gene. Science 1992, 258: 1938-1941.

2.      Koff, W.C., Johnson, P.R., Watkins, D.I., Burton, D.R., Lifson, J.D., Hasenkrug,  K.J., et al. HIV vaccine design: insights from live attenuated SIV vaccines. Nature Immunology 2006, 7: 19-23.