Determinants of Vaccine Immunogenicity in HIV-Infected Pregnant Women: Analysis of B and T Cell Responses to Pandemic H1N1 Monovalent Vaccine

Year: 2015

Type: article

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.

Source: PLoS ONE

DOI: 10.1371/journal.pone.0122431

Authors: Adriana Weinberg, Petronella Muresan, Kelly M. Richardson, Terence Fenton, Teresa Dominguez, Anthony Bloom, D. Heather Watts, Mark J. Abzug, Sharon A. Nachman, Myron J. Levin, for the P1086 team

Institutions: University of Colorado Anschutz, Harvard University, Frontier Science & Technology Research Foundation, Inc., Eunice Kennedy Shriver National Institute of Child Health and Human Development, State University of New York, Stony Brook University

Language: English

Topic: Influenza Virus Research Studies

Subfield: Epidemiology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $2,382

Funders: U.S. Department of State, University of Southern California, Children's Hospital of Philadelphia, University of Miami, Texas Children's Hospital, State University of New York, University of Washington, Tulane University, Johns Hopkins University, Dartmouth College, Rush University, University of South Florida, Seattle Children's Research Institute, International Maternal Pediatric Adolescent AIDS Clinical Trials Network, National Institutes of Health, Centers for Disease Control and Prevention, University of California, San Diego, University of California, San Francisco, University of Colorado Denver, National Institute of Mental Health, National Institute of Allergy and Infectious Diseases, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Child Health and Human Development, National Center for Advancing Translational Sciences, Eunice Kennedy Shriver National Institute of Child Health and Human Development

OpenAlex ID: W2019422839