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.

Premature ageing of the immune system relates to increased anti-lymphocyte antibodies (ALA) after an immunization in HIV-1-infected and kidney-transplanted patients

“…Interestingly, among all individuals who did not increase (Delta − ) the ALA titres after vaccination, higher levels of B cell IL-21R expression and plasma IL-21 with lower levels of MA and DN were observed compared to individuals who had an increased (Delta + ). Moreover, while a direct correlation was found between B cell IL-21R expression and ALA titres before vaccination, this reversed after vaccination, thus reinforcing the positive role indicated previously for the B cell IL-21R during vaccination [14]. The frequencies of both MA and DN correlated directly with the ALA titres after vaccination and inversely to B cell IL-21R expression.…”

“…It has been reported recently that the up-regulation of IL-21 receptor (R) on B cells and of plasma IL-21 levels could distinguish among A(H1N1)pdm09 vaccine responders and non-responders [14]. Thus, in order to assess whether the ALA increase observed in the HIV and KT groups after flu immunization, related to a different activation status of B cells or to a different degree of immune senescence in these groups, the B cell IL-21R expression and the frequencies of mature-activated (CD10 cells was significantly higher in the HC group compared to HIV and KT (P < 0·0001), with the lowest level observed in the HIV group compared to KT (P = 0·02) (Fig.…”

SIV infection of rhesus macaques results in dysfunctional T- and B-cell responses to neo and recall Leishmania major vaccination

“…54 Consistent with this premise, previous studies have shown decreased serum IL-21 and IL-21 production by T cells from HIV-infected individuals. 55,56 Although we found no difference in expression of IL-21 among Tfh cells from LNs of SIV-uninfected and SIV-infected RMs, preferential infection of Tfh cells could alter the overall functionality of these cells, thereby potentially affecting the ability to mount appropriate adaptive immune responses.…”

Immune reconstitution and vaccination outcome in HIV-1 infected children

“…For example, one of these studies proposed upregulation of the interleukin (IL)-21 receptor on B-cells and of IL-21 in plasma as a novel immunological marker to distinguish between 2009 pandemic flu vaccine responders and non-responders. 90 This may suggest that additional immunonological markers, rather than antibody response, may be used for evaluating clinical protection in the HIV-1 infected pediatric population.…”