HIV infection worsens age-associated defects in antibody responses to influenza vaccine

Varghese K. George, Suresh Pallikkuth, Anita Parmigiani, Maria L Alcaide, Margaret A Fischl, Kristopher Arheart, Savita G Pahwa

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Background. Antibody responses to seasonal influenza vaccines are defective during older age and human immunodeficiency virus (HIV) infection. The effect of HIV on immune function in aging is relatively unknown. Methods. HIV-infected and HIV-uninfected young women (age, 19-54 years) and older women (age, >55 years) were evaluated for B-cell and T-cell responses before and 4 weeks after influenza vaccination. Results. Frequencies of seroprotection pre-vaccination and vaccine responsiveness (≥ 4-fold increase in antibody titer) were lower in HIV-infected participants than in age-matched HIV-uninfected participants. A subgroup of vaccine nonresponders were compared to responders and found to have reduced frequencies of memory B cells and antigen-specific antibody-secreting cells after vaccination. Frequencies of peripheral T-follicular helper (pTfh) cells correlated with memory B-cell function and influenza A(H1N1) antibody titers. Serologic and immunologic deficits were most frequent in older HIV-infected participants. Underlying CD4<sup>+</sup> T-cell immune activation and inflammation correlated negatively with antibody titers and B-cell function, which was not enhanced by exogenous interleukin 21 supplementation in HIV-infected, older vaccine nonresponders. Conclusions. Immune activation associated with HIV infection and impaired pTfh function heighten deficiencies in antibody responses to influenza vaccine in older individuals. Strategies to reduce immune activation or augment pTfh function may enhance antibody responses in the aging HIV-infected population.

Original languageEnglish (US)
Pages (from-to)1959-1968
Number of pages10
JournalJournal of Infectious Diseases
Volume211
Issue number12
DOIs
StatePublished - Jun 15 2015

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Influenza Vaccines
Virus Diseases
Antibody Formation
HIV
B-Lymphocytes
Vaccination
Vaccines
Human Influenza
Antibodies
T-Lymphocytes
Antibody-Producing Cells
Helper-Inducer T-Lymphocytes
Inflammation
Antigens

Keywords

  • aging
  • CD4 T-cell immune activation
  • HIV infection
  • IL-21
  • inflammation
  • memory B cells
  • peripheral T follicular helper cells
  • seasonal influenza vaccination

ASJC Scopus subject areas

  • Infectious Diseases
  • Immunology and Allergy

Cite this

HIV infection worsens age-associated defects in antibody responses to influenza vaccine. / George, Varghese K.; Pallikkuth, Suresh; Parmigiani, Anita; Alcaide, Maria L; Fischl, Margaret A; Arheart, Kristopher; Pahwa, Savita G.

In: Journal of Infectious Diseases, Vol. 211, No. 12, 15.06.2015, p. 1959-1968.

Research output: Contribution to journalArticle

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abstract = "Background. Antibody responses to seasonal influenza vaccines are defective during older age and human immunodeficiency virus (HIV) infection. The effect of HIV on immune function in aging is relatively unknown. Methods. HIV-infected and HIV-uninfected young women (age, 19-54 years) and older women (age, >55 years) were evaluated for B-cell and T-cell responses before and 4 weeks after influenza vaccination. Results. Frequencies of seroprotection pre-vaccination and vaccine responsiveness (≥ 4-fold increase in antibody titer) were lower in HIV-infected participants than in age-matched HIV-uninfected participants. A subgroup of vaccine nonresponders were compared to responders and found to have reduced frequencies of memory B cells and antigen-specific antibody-secreting cells after vaccination. Frequencies of peripheral T-follicular helper (pTfh) cells correlated with memory B-cell function and influenza A(H1N1) antibody titers. Serologic and immunologic deficits were most frequent in older HIV-infected participants. Underlying CD4+ T-cell immune activation and inflammation correlated negatively with antibody titers and B-cell function, which was not enhanced by exogenous interleukin 21 supplementation in HIV-infected, older vaccine nonresponders. Conclusions. Immune activation associated with HIV infection and impaired pTfh function heighten deficiencies in antibody responses to influenza vaccine in older individuals. Strategies to reduce immune activation or augment pTfh function may enhance antibody responses in the aging HIV-infected population.",
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N2 - Background. Antibody responses to seasonal influenza vaccines are defective during older age and human immunodeficiency virus (HIV) infection. The effect of HIV on immune function in aging is relatively unknown. Methods. HIV-infected and HIV-uninfected young women (age, 19-54 years) and older women (age, >55 years) were evaluated for B-cell and T-cell responses before and 4 weeks after influenza vaccination. Results. Frequencies of seroprotection pre-vaccination and vaccine responsiveness (≥ 4-fold increase in antibody titer) were lower in HIV-infected participants than in age-matched HIV-uninfected participants. A subgroup of vaccine nonresponders were compared to responders and found to have reduced frequencies of memory B cells and antigen-specific antibody-secreting cells after vaccination. Frequencies of peripheral T-follicular helper (pTfh) cells correlated with memory B-cell function and influenza A(H1N1) antibody titers. Serologic and immunologic deficits were most frequent in older HIV-infected participants. Underlying CD4+ T-cell immune activation and inflammation correlated negatively with antibody titers and B-cell function, which was not enhanced by exogenous interleukin 21 supplementation in HIV-infected, older vaccine nonresponders. Conclusions. Immune activation associated with HIV infection and impaired pTfh function heighten deficiencies in antibody responses to influenza vaccine in older individuals. Strategies to reduce immune activation or augment pTfh function may enhance antibody responses in the aging HIV-infected population.

AB - Background. Antibody responses to seasonal influenza vaccines are defective during older age and human immunodeficiency virus (HIV) infection. The effect of HIV on immune function in aging is relatively unknown. Methods. HIV-infected and HIV-uninfected young women (age, 19-54 years) and older women (age, >55 years) were evaluated for B-cell and T-cell responses before and 4 weeks after influenza vaccination. Results. Frequencies of seroprotection pre-vaccination and vaccine responsiveness (≥ 4-fold increase in antibody titer) were lower in HIV-infected participants than in age-matched HIV-uninfected participants. A subgroup of vaccine nonresponders were compared to responders and found to have reduced frequencies of memory B cells and antigen-specific antibody-secreting cells after vaccination. Frequencies of peripheral T-follicular helper (pTfh) cells correlated with memory B-cell function and influenza A(H1N1) antibody titers. Serologic and immunologic deficits were most frequent in older HIV-infected participants. Underlying CD4+ T-cell immune activation and inflammation correlated negatively with antibody titers and B-cell function, which was not enhanced by exogenous interleukin 21 supplementation in HIV-infected, older vaccine nonresponders. Conclusions. Immune activation associated with HIV infection and impaired pTfh function heighten deficiencies in antibody responses to influenza vaccine in older individuals. Strategies to reduce immune activation or augment pTfh function may enhance antibody responses in the aging HIV-infected population.

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