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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.

SUBMITTER: Fukazawa Y

PROVIDER: S-EPMC3493820 | biostudies-literature | 2012 Nov

REPOSITORIES: biostudies-literature

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

Fukazawa Yoshinori Y Park Haesun H Cameron Mark J MJ Lefebvre Francois F Lum Richard R Coombes Noel N Mahyari Eisa E Hagen Shoko I SI Bae Jin Young JY Reyes Marcelo Delos MD Swanson Tonya T Legasse Alfred W AW Sylwester Andrew A Hansen Scott G SG Smith Andrew T AT Stafova Petra P Shoemaker Rebecca R Li Yuan Y Oswald Kelli K Axthelm Michael K MK McDermott Adrian A Ferrari Guido G Montefiori David C DC Edlefsen Paul T PT Piatak Michael M Lifson Jeffrey D JD Sékaly Rafick P RP Picker Louis J LJ

Nature medicine 20120909 11

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 b ...[more]

PMID: 22961108

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Project description:Two herpes zoster (HZ) vaccines licensed in the United States are recommended by the Advisory Committee on Immunization Practices (ACIP): (i) live-attenuated vaccine (ZVL) using vOka strain varicella-zoster virus (VZV) and (ii) recombinant adjuvanted vaccine (RZV) containing recombinant varicella-zoster virus (VZV) glycoprotein E (gE). Two phase 3 clinical trials of RZV led the Advisory Committee on Immunization Practices (ACIP) to recommend it with preferred status. VZV T cell-mediated immunity (CMI), but not humoral immunity, is considered essential for protection against HZ. Published studies of humoral immunity focused on VZV-specific IgG concentration. To complement reports comparing the CMI responses to these vaccines, we compared humoral responses in ZVL and RZV recipients, emphasizing functional qualities (avidity and neutralization). Baseline avidities to a VZV glycoprotein mixture (gp) were near the upper limit of detection, but avidity to gE was much lower. Small increases in gp avidity were observed for both RZV and ZVL vaccination (19 and 12 avidity index units [AIU], respectively). RZV boosted both gE avidity and VZV neutralizing antibody significantly more than ZVL (mean gE avidity boost, 47 AIU versus 22 AIU; mean neutralizing antibody boost, 22-fold versus 8-fold). Increases in neutralizing antibodies strongly correlated with gE avidity increases (r = 0.5) and moderately with gp avidity increases (r = 0.23). After 1 year, 81% of RZV recipients and only 18% of ZVL recipients retained >50% of their peak avidity boosts. These results are consistent with the CMI responses to these vaccines: RZV responses are skewed to long-term memory, whereas ZVL preferentially induces transient effector responses.IMPORTANCE These observations further distinguish the immunogenicity and duration of the immune response of the two vaccines. In addition, measurements of functional humoral immunity (IgG avidity and neutralizing antibody) in response to zoster immunization, alone or combined with other immune markers, might contribute to practical in vitro correlates of protection. Combined with previous observations of the cell-mediated response to these vaccines, this study suggests that vaccine development will benefit from more expansive and granular assessments of acquired immunity during early phase 1 immunogenicity trials.

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

Publications

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

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