Heterogeneity of T Cell Responses to Pandemic pH1N1 Monovalent Vaccine in HIV-Infected Pregnant Women

Abstract

We investigated the Th1 protective and regulatory T and B cell (Treg and Breg) responses to pH1N1 monovalent influenza vaccine (IIV1) in HIV-infected pregnant women on combination antiretroviral therapy (cART). Peripheral blood mononuclear cells (PBMCs) from 52 study participants were cryopreserved before and after vaccination and analyzed by flow cytometry. pH1N1-specific Th1, Treg, and Breg responses were measured in PBMCs after in vitro stimulation with pH1N1 and control antigen. The cohort analysis did not detect changes in pH1N1-Th1, Treg, or Breg subsets postvaccination. However, individual analyses distinguished subjects who mounted vigorous Th1 responses postvaccination from others who did not. Postvaccination, high pH1N1-Th1 correlated with high pH1N1-Treg and Breg responses, suggesting that low influenza effector responses did not result from excessive vaccine-induced immune regulation. High postvaccination pH1N1-Th1 responses correlated with baseline high PHA- and pH1N1-IFN-γ ELISpot and circulating CD4(+)CD39(+)% and CD8(+)CD39(+)% Treg, with low CD8(+) cell numbers and CD19(+)FOXP3(+)% Breg, but not with CD4(+) cell numbers or HIV viral load. These data highlight the heterogeneity of T cell responses to vaccines in HIV-infected individuals on cART. Predictors of robust Th1 responses to IIV include CD8(+) cell numbers, T cell functionality, and circulating Breg and Treg.

FIG. 1.

Correlations between change from baseline to postdose 1 in pH1N1-specific CD4⁺MIP1β⁺% and regulatory T cell subsets. Data were derived from peripheral blood mononuclear cells (PBMC) of 52 HIV-infected pregnant women collected before and 21–28 days after the administration of a double-dose of pH1N1 IIV1. Data points represent pH1N1-specific T cell subset frequencies at postvaccination after subtraction of prevaccination frequencies. The coefficients of correlations and p values measured with the Spearman correlation test shown on the graphs demonstrate highly significant associations between the changes in CD4⁺MIP1β⁺% (x axes), representing Th1 responses, in response to vaccination and selected Treg- and Breg-subset% changes (y axes) after vaccination.