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. 2015 Apr 13;10(4):e0122431.
doi: 10.1371/journal.pone.0122431. eCollection 2015.

Determinants of vaccine immunogenicity in HIV-infected pregnant women: analysis of B and T cell responses to pandemic H1N1 monovalent vaccine

Adriana Weinberg  1 , Petronella Muresan  2 , Kelly M Richardson  1 , Terence Fenton  2 , Teresa Dominguez  1 , Anthony Bloom  3 , D Heather Watts  4 , Mark J Abzug  1 , Sharon A Nachman  5 , Myron J Levin  1 ; P1086 team
Affiliations

Determinants of vaccine immunogenicity in HIV-infected pregnant women: analysis of B and T cell responses to pandemic H1N1 monovalent vaccine

Adriana Weinberg et al. PLoS One. .

Abstract

Influenza infections have high frequency and morbidity in HIV-infected pregnant women, underscoring the importance of vaccine-conferred protection. To identify the factors that determine vaccine immunogenicity in this group, we characterized the relationship of B- and T-cell responses to pandemic H1N1 (pH1N1) vaccine with HIV-associated immunologic and virologic characteristics. pH1N1 and seasonal-H1N1 (sH1N1) antibodies were measured in 119 HIV-infected pregnant women after two double-strength pH1N1 vaccine doses. pH1N1-IgG and IgA B-cell FluoroSpot, pH1N1- and sH1N1-interferon γ (IFNγ) and granzyme B (GrB) T-cell FluoroSpot, and flow cytometric characterization of B- and T-cell subsets were performed in 57 subjects. pH1N1-antibodies increased after vaccination, but less than previously described in healthy adults. pH1N1-IgG memory B cells (Bmem) increased, IFNγ-effector T-cells (Teff) decreased, and IgA Bmem and GrB Teff did not change. pH1N1-antibodies and Teff were significantly correlated with each other and with sH1N1-HAI and Teff, respectively, before and after vaccination. pH1N1-antibody responses to the vaccine significantly increased with high proportions of CD4+, low CD8+ and low CD8+HLADR+CD38+ activated (Tact) cells. pH1N1-IgG Bmem responses increased with high proportions of CD19+CD27+CD21- activated B cells (Bact), high CD8+CD39+ regulatory T cells (Treg), and low CD19+CD27-CD21- exhausted B cells (Bexhaust). IFNγ-Teff responses increased with low HIV plasma RNA, CD8+HLADR+CD38+ Tact, CD4+FoxP3+ Treg and CD19+IL10+ Breg. In conclusion, pre-existing antibody and Teff responses to sH1N1 were associated with increased responses to pH1N1 vaccination in HIV-infected pregnant women suggesting an important role for heterosubtypic immunologic memory. High CD4+% T cells were associated with increased, whereas high HIV replication, Tact and Bexhaust were associated with decreased vaccine immunogenicity. High Treg increased antibody responses but decreased Teff responses to the vaccine. The proportions of immature and transitional B cells did not affect the responses to vaccine. Increased Bact were associated with high Bmem responses to the vaccine.

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Conflict of interest statement

Competing Interests: AW receives grants from MedImmune, GSK, and SanofiPasteur. MJL receives grants from GSK and SanofiPasteur and is also a consultant for GSK. All research support goes to UC Denver Institution. This does not alter the authors’ adherence to PLOS ONE policies on sharing data and materials.

Figures

Fig 1
Fig 1. pH1N1 and sH1N1 HAI titers of HIV-infected pregnant women who received two doses of pH1N1 monovalent vaccine.
Data represent medians and inter quartile ranges of the reciprocals of the HAI titers. The number of subjects who contributed data and p values of paired comparisons are indicated on the graph. Panel A shows pH1N1 antibody titers and panel B shows sH1N1 antibody titers.
Fig 2
Fig 2. pH1N1 IgG and IgA B-cell memory responses of HIV-infected pregnant women who received two doses of pH1N1 monovalent vaccine.
Data represent medians and inter quartile ranges of antibody secreting cells (ASC)/106 PBMC. The number of subjects who had adequate numbers of viable PBMC to complete the assays at each time point is indicated on the graph. p values calculated with Wilcoxon Matched Pairs Signed-Rank test are indicated on the graph. Panel A shows IgG ASC/106 PBMC and panel B shows IgA ASC/106 PBMC.
Fig 3
Fig 3. pH1N1 and sH1N1 effector T cell responses of HIV-infected pregnant women who received two doses of pH1N1 monovalent vaccine.
Data represent medians and inter quartile ranges of spot forming cells (SFC)/106 PBMC. The number of subjects who had adequate numbers of viable PBMC to complete the assays at each time point is indicated on the graph. p values calculated with Wilcoxon Matched Pairs Signed-Rank test are indicated on the graph. Panel A shows pH1N1-IFNγ SFC/106 PBMC, panel B pH1N1-granzyme B (GrB) SFC/106 PBMC, panel C sH1N1-IFNγ SFC/106 PBMC, panel D sH1N1-GrB SFC/106 PBMC, panel E PHA-IFNγ SFC/106 PBMC positive controls, and panel F PHA-GrB SFC/106 PBMC controls.
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