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).
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 IFNγ ELISPOT responses, whose magnitude positively correlated with the baseline pH1N1, but not with seasonal H1N1 HAI titers. pH1N1-specific IFNγ 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 IFNγ ELISPOT results was marginally associated with higher pH1N1-specific CD19+FOXP3+ and CD4+TGFβ+% 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 IFNγ 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.
Department of Pediatrics; Division of Infectious Diseases; University of Colorado Denver; Aurora, CO USA.
Adriana
A
Weinberg
Petronella
P
Muresan
Terence
T
Fenton
Kelly
K
Richardson
Teresa
T
Dominguez
Anthony
A
Bloom
Elizabeth
E
Petzold
Patricia
P
Anthony
Coleen K
CK
Cunningham
Stephen A
SA
Spector
Sharon
S
Nachman
George K
GK
Siberry
Edward
E
Handelsman
Patricia M
PM
Flynn
D000293:Adolescent; D000914:Antibodies, Viral / Q000097:blood; D060151:B-Lymphocytes, Regulatory / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D058501:Enzyme-Linked Immunospot Assay; D005260:Female; D005434:Flow Cytometry; D015658:HIV Infections / Q000276:immunology*; D006385:Hemagglutination Inhibition Tests; D006801:Humans; D007108:Immune Tolerance; D016130:Immunophenotyping; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology*; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000276:immunology*; D008297:Male; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D055815:Young Adult
D000914:Antibodies, Viral; D007252:Influenza Vaccines
HIV infection; cell-mediated immunity; influenza vaccine; regulatory B cells; regulatory T cells