Innate immune defects correlate with failure of antibody responses to H1N1/09 vaccine in HIV-infected patients

Suresh Pallikkuth, Sudheesh Pilakka Kanthikeel, Sandra Y. Silva, Margaret A Fischl, Rajendra Pahwa, Savita G Pahwa

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Abstract

Background: Mechanisms underlying the failure of influenza vaccine-induced antibody responses in HIV-infected persons are poorly understood. Objective: To investigate innate immune factors regulating B-cell function in HIV-infected persons and to correlate them with serologic responses to H1N1/09 vaccine. Methods: We evaluated immunologic characteristics of 17 HIV-infected patients and 8 healthy controls (HCs) at 0, 7, and 28 days (designated T0, T1, and T2) following a single 15-μg dose of nonadjuvanted H1N1/09 influenza vaccine by using flow cytometry, ELISpot, and ELISA. All HCs and 9 patients (53%) seroconverted with >1:40 hemagglutination inhibition antibody titer at T2. Results: In vaccine responders and HCs, serum levels of BAFF (B cell-activating factor) and APRIL (a proliferation-inducing ligand) increased from T0 to T2 in conjunction with increases in frequencies of memory B cells. Concurrently, receptors for these factors showed changes, with increases in expression of TACI (transmembrane activator and calcium modulator and cyclophilin ligand interactor) and decreases in BAFF receptor in memory B cells. IL-2 secreting cells and IgG antibody-secreting cells increased at T2 in vaccine responders and HCs in ex vivo H1N1 antigen-stimulated cultures. These immunologic responses were not evident at T1 and were deficient in vaccine nonresponder patients at T2. At T0, vaccine nonresponders had lower frequencies of BAFF receptor and TACI-expressing memory B cells than did responders. Conclusion: Impaired memory B-cell responses, deficiencies in serum BAFF and APRIL, and alterations in their receptors on B cells were associated with failure of H1N1/09 influenza vaccine responses among virologically controlled HIV-infected patients.

Original languageEnglish
Pages (from-to)1279-1285
Number of pages7
JournalJournal of Allergy and Clinical Immunology
Volume128
Issue number6
DOIs
StatePublished - Dec 1 2011

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AIDS Vaccines
Antibody Formation
B-Lymphocytes
Vaccines
Influenza Vaccines
B-Cell Activation Factor Receptor
HIV
Ligands
B-Cell Activating Factor
Cyclophilins
Antibody-Producing Cells
Immunologic Factors
Hemagglutination
Serum
Interleukin-2
Flow Cytometry
Immunoglobulin G
Enzyme-Linked Immunosorbent Assay
Calcium
Antigens

Keywords

  • 2009 H1N1 vaccination and HIV
  • B-cell defect in HIV
  • BAFF-binding receptors and HIV
  • innate immune defect and HIV
  • T-independent humoral immune factors

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Innate immune defects correlate with failure of antibody responses to H1N1/09 vaccine in HIV-infected patients. / Pallikkuth, Suresh; Kanthikeel, Sudheesh Pilakka; Silva, Sandra Y.; Fischl, Margaret A; Pahwa, Rajendra; Pahwa, Savita G.

In: Journal of Allergy and Clinical Immunology, Vol. 128, No. 6, 01.12.2011, p. 1279-1285.

Research output: Contribution to journalArticle

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abstract = "Background: Mechanisms underlying the failure of influenza vaccine-induced antibody responses in HIV-infected persons are poorly understood. Objective: To investigate innate immune factors regulating B-cell function in HIV-infected persons and to correlate them with serologic responses to H1N1/09 vaccine. Methods: We evaluated immunologic characteristics of 17 HIV-infected patients and 8 healthy controls (HCs) at 0, 7, and 28 days (designated T0, T1, and T2) following a single 15-μg dose of nonadjuvanted H1N1/09 influenza vaccine by using flow cytometry, ELISpot, and ELISA. All HCs and 9 patients (53{\%}) seroconverted with >1:40 hemagglutination inhibition antibody titer at T2. Results: In vaccine responders and HCs, serum levels of BAFF (B cell-activating factor) and APRIL (a proliferation-inducing ligand) increased from T0 to T2 in conjunction with increases in frequencies of memory B cells. Concurrently, receptors for these factors showed changes, with increases in expression of TACI (transmembrane activator and calcium modulator and cyclophilin ligand interactor) and decreases in BAFF receptor in memory B cells. IL-2 secreting cells and IgG antibody-secreting cells increased at T2 in vaccine responders and HCs in ex vivo H1N1 antigen-stimulated cultures. These immunologic responses were not evident at T1 and were deficient in vaccine nonresponder patients at T2. At T0, vaccine nonresponders had lower frequencies of BAFF receptor and TACI-expressing memory B cells than did responders. Conclusion: Impaired memory B-cell responses, deficiencies in serum BAFF and APRIL, and alterations in their receptors on B cells were associated with failure of H1N1/09 influenza vaccine responses among virologically controlled HIV-infected patients.",
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AU - Pallikkuth, Suresh

AU - Kanthikeel, Sudheesh Pilakka

AU - Silva, Sandra Y.

AU - Fischl, Margaret A

AU - Pahwa, Rajendra

AU - Pahwa, Savita G

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AB - Background: Mechanisms underlying the failure of influenza vaccine-induced antibody responses in HIV-infected persons are poorly understood. Objective: To investigate innate immune factors regulating B-cell function in HIV-infected persons and to correlate them with serologic responses to H1N1/09 vaccine. Methods: We evaluated immunologic characteristics of 17 HIV-infected patients and 8 healthy controls (HCs) at 0, 7, and 28 days (designated T0, T1, and T2) following a single 15-μg dose of nonadjuvanted H1N1/09 influenza vaccine by using flow cytometry, ELISpot, and ELISA. All HCs and 9 patients (53%) seroconverted with >1:40 hemagglutination inhibition antibody titer at T2. Results: In vaccine responders and HCs, serum levels of BAFF (B cell-activating factor) and APRIL (a proliferation-inducing ligand) increased from T0 to T2 in conjunction with increases in frequencies of memory B cells. Concurrently, receptors for these factors showed changes, with increases in expression of TACI (transmembrane activator and calcium modulator and cyclophilin ligand interactor) and decreases in BAFF receptor in memory B cells. IL-2 secreting cells and IgG antibody-secreting cells increased at T2 in vaccine responders and HCs in ex vivo H1N1 antigen-stimulated cultures. These immunologic responses were not evident at T1 and were deficient in vaccine nonresponder patients at T2. At T0, vaccine nonresponders had lower frequencies of BAFF receptor and TACI-expressing memory B cells than did responders. Conclusion: Impaired memory B-cell responses, deficiencies in serum BAFF and APRIL, and alterations in their receptors on B cells were associated with failure of H1N1/09 influenza vaccine responses among virologically controlled HIV-infected patients.

KW - 2009 H1N1 vaccination and HIV

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KW - T-independent humoral immune factors

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