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)

Adriana Weinberg, Petronella Muresan, Terence Fenton, Kelly Richardson, Teresa Dominguez, Anthony Bloom, Elizabeth Petzold, Patricia Anthony, Coleen K. Cunningham, Stephen A. Spector, Sharon Nachman, George K. Siberry, Edward Handelsman, Patricia M. Flynn

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)957-968
Number of pages12
JournalHuman Vaccines and Immunotherapeutics
Volume9
Issue number5
DOIs
StatePublished - May 2013
Externally publishedYes

Fingerprint

Regulatory B-Lymphocytes
Enzyme-Linked Immunospot Assay
Influenza Vaccines
Regulatory T-Lymphocytes
HIV
Hemagglutination
Vaccination
Human Influenza
Flow Cytometry
AIDS Vaccines
Inactivated Vaccines
Pandemics
Vaccines
Antibodies

Keywords

  • Cell-mediated immunity
  • HIV infection
  • Influenza vaccine
  • Regulatory B cells
  • Regulatory T cells

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Pharmacology

Cite this

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). / 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.

In: Human Vaccines and Immunotherapeutics, Vol. 9, No. 5, 05.2013, p. 957-968.

Research output: Contribution to journalArticle

Weinberg, A, Muresan, P, Fenton, T, Richardson, K, Dominguez, T, Bloom, A, Petzold, E, Anthony, P, Cunningham, CK, Spector, SA, Nachman, S, Siberry, GK, Handelsman, E & Flynn, PM 2013, '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)', Human Vaccines and Immunotherapeutics, vol. 9, no. 5, pp. 957-968. https://doi.org/10.4161/hv.23774
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. / 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). In: Human Vaccines and Immunotherapeutics. 2013 ; Vol. 9, No. 5. pp. 957-968.
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abstract = "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.",
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AU - Weinberg, Adriana

AU - Muresan, Petronella

AU - Fenton, Terence

AU - Richardson, Kelly

AU - Dominguez, Teresa

AU - Bloom, Anthony

AU - Petzold, Elizabeth

AU - Anthony, Patricia

AU - Cunningham, Coleen K.

AU - Spector, Stephen A.

AU - Nachman, Sharon

AU - Siberry, George K.

AU - Handelsman, Edward

AU - Flynn, Patricia M.

PY - 2013/5

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N2 - 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.

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KW - Cell-mediated immunity

KW - HIV infection

KW - Influenza vaccine

KW - Regulatory B cells

KW - Regulatory T cells

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