title: Upregulation of IL-21 receptor on B cells and IL-21 secretion distinguishes novel 2009 H1N1 vaccine responders from nonresponders among HIV-infected persons on combination antiretroviral therapy.
abstract: Mechanisms underlying failure of novel 2009 H1N1 influenza vaccine-induced Ab responses in HIV-infected persons are poorly understood. This study prospectively evaluated 16 HIV-infected patients on combination antiretroviral therapy and eight healthy controls (HC) who received a single 15 μg dose of nonadjuvanted novel 2009 H1N1 influenza vaccine during the 2009 H1N1 epidemic. Peripheral blood was collected at baseline (T0) and at 7 d (T1) and 28 d (T2) postvaccination for evaluation of immune responses. Prevaccination hemagglutination inhibition Ab titer was <1:20 in all except one study participant. At T2, all HC and 8 out of 16 patients (50%) developed a vaccine-induced Ab titer of ≥ 1:40. Vaccine responder (R) and vaccine nonresponder patients were comparable at T0 in age, CD4 counts, virus load, and B cell immunophenotypic characteristics. At T2, HC and R patients developed an expansion of phenotypic and functional memory B cells and ex vivo H1N1-stimulated IgG Ab-secreting cells in an ELISPOT assay. The memory B cell response was preceded by a significant expansion of plasmablasts and spontaneous H1N1-specific Ab-secreting cells at T1. At T2, HC and R patients also exhibited significant increases in serum IL-21 levels and in the frequency and mean fluorescence intensity of IL-21R-expressing B cells, which correlated with serum H1N1 Ab titers. Vaccine nonresponder patients failed to develop the above-described vaccine-induced immunologic responses. The novel association of novel 2009 H1N1 vaccine-induced Ab responses with IL-21/IL-21R upregulation and with development of memory B cells and plasmablasts has implications for future research in vaccine design.
authors.affiliation: Department of Microbiology and Immunology, University of Miami Miller School of Medicine, Miami, FL 33136, USA.
authors.forename: Suresh
authors.initials: S
authors.lastname: Pallikkuth
authors.forename: Sudheesh
authors.initials: S
authors.lastname: Pilakka Kanthikeel
authors.forename: Sandra Y
authors.initials: SY
authors.lastname: Silva
authors.forename: Margaret
authors.initials: M
authors.lastname: Fischl
authors.forename: Rajendra
authors.initials: R
authors.lastname: Pahwa
authors.forename: Savita
authors.initials: S
authors.lastname: Pahwa
mesh_terms: D000328:Adult; D000368:Aged; D019380:Anti-HIV Agents / Q000627:therapeutic use; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D004359:Drug Therapy, Combination; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy*; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D007156:Immunologic Memory / Q000276:immunology; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology*; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000276:immunology*; D007251:Influenza, Human / Q000097:blood / Q000150:complications / Q000276:immunology; D007378:Interleukins / Q000097:blood / Q000276:immunology* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010950:Plasma Cells / Q000276:immunology / Q000378:metabolism; D011446:Prospective Studies; D053655:Receptors, Interleukin-21 / Q000276:immunology* / Q000378:metabolism; D013997:Time Factors; D015854:Up-Regulation; D055815:Young Adult; D000098546:Interleukin-21
chemical_list: D019380:Anti-HIV Agents; D000914:Antibodies, Viral; D007074:Immunoglobulin G; D007252:Influenza Vaccines; D007378:Interleukins; D053655:Receptors, Interleukin-21; D000098546:Interleukin-21