title: Determinants of vaccine immunogenicity in HIV-infected pregnant women: analysis of B and T cell responses to pandemic H1N1 monovalent vaccine.
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.
authors: University of Colorado Anschutz Medical Center, Aurora, Colorado, United States of America.
authors: Adriana
authors: A
authors: Weinberg
authors: Statistical and Data Analysis Center, Center for Biostatistics in AIDS Research, Harvard School of Public Health, Boston, Massachusetts, United States of America.
authors: Petronella
authors: P
authors: Muresan
authors: University of Colorado Anschutz Medical Center, Aurora, Colorado, United States of America.
authors: Kelly M
authors: KM
authors: Richardson
authors: Statistical and Data Analysis Center, Center for Biostatistics in AIDS Research, Harvard School of Public Health, Boston, Massachusetts, United States of America.
authors: Terence
authors: T
authors: Fenton
authors: University of Colorado Anschutz Medical Center, Aurora, Colorado, United States of America.
authors: Teresa
authors: T
authors: Dominguez
authors: Frontier Science and Technology Research Foundation, Buffalo, New York, United States of America.
authors: Anthony
authors: A
authors: Bloom
authors: Maternal and Pediatric Infectious Disease Branch, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Maryland, United States of America.
authors: D Heather
authors: DH
authors: Watts
authors: University of Colorado Anschutz Medical Center, Aurora, Colorado, United States of America.
authors: Mark J
authors: MJ
authors: Abzug
authors: State University of New York Health Science Center at Stony Brook, Stony Brook, New York, United States of America.
authors: Sharon A
authors: SA
authors: Nachman
authors: University of Colorado Anschutz Medical Center, Aurora, Colorado, United States of America.
authors: Myron J
authors: MJ
authors: Levin
mesh_terms: D000328:Adult; D000914:Antibodies, Viral / Q000276:immunology; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000276:immunology* / Q000473:pathology; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology / Q000472:pathogenicity; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000276:immunology*; D007251:Influenza, Human / Q000150:complications / Q000276:immunology* / Q000473:pathology; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000276:immunology* / Q000517:prevention & control; D016176:T-Lymphocyte Subsets / Q000276:immunology
chemical_list: D000914:Antibodies, Viral; D007252:Influenza Vaccines