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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 ?g 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.

SUBMITTER: Pallikkuth S

PROVIDER: S-EPMC3170914 | biostudies-literature | 2011 Jun

REPOSITORIES: biostudies-literature

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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.

Pallikkuth Suresh S Pilakka Kanthikeel Sudheesh S Silva Sandra Y SY Fischl Margaret M Pahwa Rajendra R Pahwa Savita S

Journal of immunology (Baltimore, Md. : 1950) 20110429 11

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 r ...[more]

PMID: 21531891

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Project description:BackgroundTo compare the cost-effectiveness of treating early responders versus early nonresponders to an atypical antipsychotic (risperidone) and the cost-effectiveness of treating early nonresponders maintained on risperidone versus those switched to olanzapine.MethodsThis post hoc analysis used data from a randomized, double-blind, 12-week schizophrenia study (Study Code: HGMN, n = 628). Participants were initially assigned to risperidone therapy. Early response was defined as a ≥ 20% improvement on the Positive and Negative Syndrome Scale (PANSS) total score from baseline to two weeks. Early responders continued on risperidone, whereas early nonresponders were randomized in a double-blind manner to continue on risperidone or switch to olanzapine for 10 additional weeks. Early responders and early nonresponders maintained on risperidone were compared for health-state utilities (benefits) and total cost over the 12-week study; early nonresponders maintained on risperidone or switched to olanzapine were compared from randomization (10-week period). Utilities were derived from the PANSS and adverse events. Mixed models were used to assess group differences in utilities. Treatment costs were calculated based on health states. Incremental cost-effectiveness ratios were then utilized to compare treatment groups.ResultsEarly responders to risperidone had significantly greater total utility and lower total treatment costs than early nonresponders to risperidone. Compared with early nonresponders who continued on risperidone, those who were switched to olanzapine had significantly higher total utility scores at endpoint and numerically lower total treatment costs, reflecting significantly lower nonmedication treatment costs, even though medication costs were significantly higher compared with generic risperidone.ConclusionTreatment of early responders was more cost-effective than treatment of early nonresponders to atypical antipsychotic therapy. Switching early nonresponders to olanzapine resulted in improved treatment effectiveness, met the criteria for some dominance, and appeared modestly more cost-effective than maintaining treatment with generic risperidone.

Dataset Information

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.

Publications

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.

Similar Datasets

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