IgA ASCs were barely detectable at baseline (median = 1 ASC/106 PBMC) and did not significantly increase after vaccination (Fig 2B)
IgA ASCs were barely detectable at baseline (median = 1 ASC/106 PBMC) and did not significantly increase after vaccination (Fig 2B). Open in a separate window 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. committee for data access requests. 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, 5-(N,N-Hexamethylene)-amiloride 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 (IFN) 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, IFN-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). IFN-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, 5-(N,N-Hexamethylene)-amiloride 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. Introduction Pregnant women in their 2nd and 3rd trimesters and the first 2 weeks post-partum have a 3.3- to 5.5-fold greater risk of hospitalization for influenza-associated acute cardio-respiratory illness compared to non-pregnant women[1C6]. Additionally, influenza respiratory illness during pregnancy may increase the risk of premature delivery, fetal distress and emergency caesarean sections[7,8]. Heightened susceptibility to severe influenza illness during pregnancy is particularly evident during influenza pandemics as was observed during the pandemic caused by the pandemic influenza A H1N1 2009 (pH1N1)[1C3,5]. Vaccination is the most effective modality to combat the morbidity of influenza infections[9,10]. Administration of seasonal trivalent inactivated vaccines (IIV3) to pregnant women prevents severe infections in women and their infants up to 6 months of life and decreases premature deliveries[10C16]. Although early studies showed that IIV3 had similar immunogenicity in pregnant women and non-pregnant adults, this concept was recently challenged[18,19]. 5-(N,N-Hexamethylene)-amiloride HIV-infected adults do Mouse monoclonal to SYP not seem to have greater influenza-associated morbidity than same-age uninfected controls except for those with CD4+ cells 200 cells/L[20C26]. This conclusion is uncertain with respect to HIV-infected pregnant women in whom the immunosuppressive effect of pregnancy may synergize with that of HIV infection. Furthermore, the immunogenicity of influenza vaccines is much lower in HIV-infected individuals compared with uninfected controls of the same age. We previously showed that HIV-infected pregnant women had lower hemagglutination inhibition (HAI) antibodies and cell-mediated immunity (CMI) in response to IIV3 compared with uninfected pregnant women. Since low CD4+ cell numbers have been associated with poor responses to vaccines in HIV-infected individuals [28C37], it is noteworthy that HIV-infected pregnant women experience a decrease.