TY - JOUR
T1 - B and T cell phenotypic profiles of African HIV-infected and HIV-exposed uninfected infants
T2 - Associations with antibody responses to the pentavalent rotavirus vaccine
AU - The P1072 and Tshipidi Study Teams
AU - Weinberg, Adriana
AU - Lindsey, Jane
AU - Bosch, Ronald
AU - Persaud, Deborah
AU - Sato, Paul
AU - Ogwu, Anthony
AU - Asmelash, Aida
AU - Bwakura-Dangarambezi, Mutsa
AU - Chi, Benjamin H.
AU - Canniff, Jennifer
AU - Lockman, Shahin
AU - Gaseitsiwe, Simani
AU - Moyo, Sikhulile
AU - Smith, Christiana Elizabeth
AU - Moraka, Natasha O.
AU - Levin, Myron J.
N1 - Funding Information:
We gratefully acknowledge the contributions of the site investigators and site staffwho conducted the P1072 study: Gaborone Prevention/Treatment Trials CRS: Charles Fane RN/MW, Dudu Kooreng RN, Tebogo J. Kakhu BSN, RN/MW, Loeto Mazhani MD; Molepolole Prevention/Treatment Trials CRS: Tumalano Sekoto BSN, RN/MW, Lesedi Tirelo RN, Tshepo T. Frank BPharm, Mpho Raesi BSN; Kilimanjaro Christian Medical CRS: Grace Kinabo MD, PhD, Boniface Njau MPH, Anne Buchanan MD, MPH, Janeth Kimaro RN; George Clinic CRS: Felistus Mbewe RN, BSc, Ellen Shingalili RN, Fyatilani Chirwa RN, Helen Bwalya Mulenga BPharm, MBA; Harare Family Care CRS: Tapiwa Mbengeranwa MBChB, Taurai Beta MBChB, Ethel Dauya MPH, Hilda Mujuru MBChB, MMed, MSc. We thank Kelly M Richardson and Teresa Dominguez for technical support and Michelle Brown for contributing to the protocol development. Overall support for the International Maternal Pediatric Adolescent AIDS Clinical Trials Group (IMPAACT) was provided by the National Institute of Allergy and Infectious Diseases (NIAID) of the National Institutes of Health (NIH) under Award Numbers UM1AI068632 (IMPAACT LOC), UM1AI068616 (IMPAACT SDMC), and UM1AI106716 (IMPAACT LC), with co-funding from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) and the National Institute of Mental Health (NIMH). The laboratory work was funded by NICHD through contract N01HD33162. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. Merck & Co., Inc., provided vaccine and financial support for laboratory assays.
Publisher Copyright:
© 2018 Weinberg, Lindsey, Bosch, Persaud, Sato, Ogwu, Asmelash, Bwakura-Dangarambezi, Chi, Canniff, Lockman, Gaseitsiwe, Moyo, Smith, Moraka and Levin.
PY - 2018/1/19
Y1 - 2018/1/19
N2 - We examined associations between B and T cell phenotypic profiles and antibody responses to the pentavalent rotavirus vaccine (RV5) in perinatally HIV-infected (PHIV) infants on antiretroviral therapy and in HIV-exposed uninfected (PHEU) infants enrolled in International Maternal Pediatric Adolescent AIDS Clinical Trials P1072 study (NCT00880698). Of 17 B and T cell subsets analyzed, PHIV and PHEU differed only in the number of CD4+ T cells and frequency of naive B cells, which were higher in PHEU than in PHIV. In contrast, the B and T cell phenotypic profiles of PHIV and PHEU markedly differed from those of geographically matched contemporary HIV-unexposed infants. The frequency of regulatory T and B cells (Treg, Breg) of PHIV and PHEU displayed two patterns of associations: FOXP3+ CD25+ Treg positively correlated with CD4+ T cell numbers; while TGFβ+ Treg and IL10+ Treg and Breg positively correlated with the frequencies of inflammatory and activated T cells. Moreover, the frequencies of activated and inflammatory T cells of PHIV and PHEU positively correlated with the frequency of immature B cells. Correlations were not affected by HIV status and persisted over time. PHIV and PHEU antibody responses to RV5 positively correlated with CD4+ T cell counts and negatively with the proportion of immature B cells, similarly to what has been previously described in chronic HIV infection. Unique to PHIV and PHEU, anti-RV5 antibodies positively correlated with CD4+/CD8+FOXP3+CD25+% and negatively with CD4+IL10+% Tregs. In conclusion, PHEU shared with PHIV abnormal B and T cell phenotypic profiles. PHIV and PHEU antibody responses to RV5 were modulated by typical HIV-associated immune response modifiers except for the association between CD4+/CD8+FOXP3+CD25+Treg and increased antibody production.
AB - We examined associations between B and T cell phenotypic profiles and antibody responses to the pentavalent rotavirus vaccine (RV5) in perinatally HIV-infected (PHIV) infants on antiretroviral therapy and in HIV-exposed uninfected (PHEU) infants enrolled in International Maternal Pediatric Adolescent AIDS Clinical Trials P1072 study (NCT00880698). Of 17 B and T cell subsets analyzed, PHIV and PHEU differed only in the number of CD4+ T cells and frequency of naive B cells, which were higher in PHEU than in PHIV. In contrast, the B and T cell phenotypic profiles of PHIV and PHEU markedly differed from those of geographically matched contemporary HIV-unexposed infants. The frequency of regulatory T and B cells (Treg, Breg) of PHIV and PHEU displayed two patterns of associations: FOXP3+ CD25+ Treg positively correlated with CD4+ T cell numbers; while TGFβ+ Treg and IL10+ Treg and Breg positively correlated with the frequencies of inflammatory and activated T cells. Moreover, the frequencies of activated and inflammatory T cells of PHIV and PHEU positively correlated with the frequency of immature B cells. Correlations were not affected by HIV status and persisted over time. PHIV and PHEU antibody responses to RV5 positively correlated with CD4+ T cell counts and negatively with the proportion of immature B cells, similarly to what has been previously described in chronic HIV infection. Unique to PHIV and PHEU, anti-RV5 antibodies positively correlated with CD4+/CD8+FOXP3+CD25+% and negatively with CD4+IL10+% Tregs. In conclusion, PHEU shared with PHIV abnormal B and T cell phenotypic profiles. PHIV and PHEU antibody responses to RV5 were modulated by typical HIV-associated immune response modifiers except for the association between CD4+/CD8+FOXP3+CD25+Treg and increased antibody production.
KW - AIDS
KW - Antibodies
KW - B cells
KW - Human
KW - T cells
KW - Vaccination
UR - http://www.scopus.com/inward/record.url?scp=85040808768&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85040808768&partnerID=8YFLogxK
U2 - 10.3389/fimmu.2017.02002
DO - 10.3389/fimmu.2017.02002
M3 - Article
C2 - 29403482
AN - SCOPUS:85040808768
SN - 1664-3224
VL - 8
JO - Frontiers in immunology
JF - Frontiers in immunology
IS - JAN
M1 - 2002
ER -