High proportions of regulatory B and T cells are associated with decreased cellular responses to pH1N1 influenza vaccine in HIV-infected children and youth (IMPAACT P1088)
UMass Center for Clinical and Translational Science
Immunology and Infectious Disease | Infectious Disease | Influenza Humans | Influenza Virus Vaccines | Pediatrics | Translational Medical Research
HIV-infected individuals have poor responses to inactivated influenza vaccines. To evaluate the potential role of regulatory T (Treg) and B cells (Breg), we analyzed their correlation with humoral and cell-mediated immune (CMI) responses to pandemic influenza (pH1N1) monovalent vaccine in HIV-infected children and youth. Seventy-four HIV-infected, 4- to 25-y old participants in a 2-dose pH1N1 vaccine study had circulating and pH1N1-stimulated Treg and Breg measured by flow cytometry at baseline, post-dose 1 and post-dose 2. Concomitantly, CMI was measured by ELISPOT and flow cytometry; and antibodies by hemagglutination inhibition (HAI). At baseline, most of the participants had pH1N1-specific IFNgamma ELISPOT responses, whose magnitude positively correlated with the baseline pH1N1, but not with seasonal H1N1 HAI titers. pH1N1-specific IFNgamma ELISPOT responses did not change post-dose 1 and significantly decreased post-dose 2. In contrast, circulating CD4+CD25+% and CD4+FOXP3+% Treg increased after vaccination. The decrease in IFNgamma ELISPOT results was marginally associated with higher pH1N1-specific CD19+FOXP3+ and CD4+TGFbeta+% Breg and Treg, respectively. In contrast, increases in HAI titers post-dose 1 were associated with significantly higher circulating CD19+CD25+% post-dose 1, whereas increases in IFNgamma ELISPOT results post-dose 1 were associated with higher circulating CD4+/C8+CD25+FOXP3+%. In conclusion, in HIV-infected children and youth, influenza-specific Treg and Breg may contribute to poor responses to vaccination. However, robust humoral and CMI responses to vaccination may result in increased circulating Treg and/or Breg, establishing a feed-back mechanism.
HIV infection, cell-mediated immunity, influenza vaccine, regulatory B cells, regulatory T cells, UMCCTS funding
DOI of Published Version
Hum Vaccin Immunother. 2013 May;9(5):957-68. doi: 10.4161/hv.23774. Epub 2013 Jan 31. Link to article on publisher's site
Human vaccines and immunotherapeutics
Weinberg, Adriana; Muresan, Petronella; Fenton, Terence; Richardson, Kelly; Dominguez, Teresa; Bloom, Anthony; Petzold, Elizabeth; Anthony, Patricia; Cunningham, Coleen K.; Spector, Stephen A.; Nachman, Sharon; Siberry, George K.; Handelsman, Edward; Flynn, Patricia M.; and IMPAACT P1088 study team, "High proportions of regulatory B and T cells are associated with decreased cellular responses to pH1N1 influenza vaccine in HIV-infected children and youth (IMPAACT P1088)" (2013). UMass Center for Clinical and Translational Science Supported Publications. 195.