Unique biomarkers for B-cell function predict the serum response to pandemic H1N1 influenza vaccine

Abstract

In order to develop predictive markers for a beneficial humoral immune response, we evaluated the in vivo and in vitro response to the pandemic (p)H1N1 vaccine in young and elderly individuals. We measured serum antibody response and associated this with the in vitro B-cell response to the vaccine, measured by activation-induced cytidine deaminase (AID). Both responses decrease with age and are significantly correlated. The percentage of switched memory B cells in blood, both before and after vaccination, is decreased with age. The percentage of switched memory B cells at t0 correlates with the hemagglutination inhibition response and therefore, we suggest that this may be used as a predictive marker for B-cell responsiveness. AID induced by CpG before vaccination also predicts the robustness of the vaccine response. Plasmablasts showed a trend to increase after vaccination in young individuals only. This report establishes molecular biomarkers of response, percentage of switched memory B cells and AID response to CpG, useful for identifying individuals at risk of poor response and also for measuring improvements in vaccines and monitoring optimal humoral responses.

Aging, cytomegalovirus (CMV) and influenza vaccine responses

“…37,38 Several studies have clearly demonstrated that the age-dependent differences in the response to influenza vaccination may be due to age-related differences in the innate and adaptive immune systems. These include decreased T cell function [39][40][41][42] and loss of CD28 expression, 39 decreased memory B cells [43][44][45][46][47][48] and reduced specificity and class of antibody produced, 49,50 reduced natural killer cell cytotoxicity on a per cell basis, 51 and reduced number and/or function of dendritic cells in blood. 42,52,53 In addition cytomegalovirus (CMV) positivity is increased with age.…”

“…44,46,77,78,79 Some of the B cell defects we have identified include a reduction in activation-induced cytidine deaminase (AID), the enzyme necessary for class switch recombination (CSR) and SHM; E47, a key transcription factor regulating AID 80 ; and the ability to generate higher affinity antibodies to a new antigen. In the last 5 influenza vaccine seasons (2009-2013), we have measured the antibody response to the seasonal and pandemic influenza vaccines in serum and we have associated this response with the B cell response after vaccination to the vaccine in vitro.…”

“…[82][83][84][85][86] Our published results have shown that the specific response of B cells to vaccination in vivo and in vitro are both decreased with age and are significantly correlated. 44,46,87 , Moreover, the percentages of switched memory B cells and CpG-induced AID before vaccination are both good B cell biomarkers that are reduced in elderly as compared to young individuals and are significantly correlated with the in vivo antibody response to the vaccine. 44,46 Therefore, we have proposed these as predictive biomarkers of optimal vaccine-induced antibody responses.…”

“…44,46,87 , Moreover, the percentages of switched memory B cells and CpG-induced AID before vaccination are both good B cell biomarkers that are reduced in elderly as compared to young individuals and are significantly correlated with the in vivo antibody response to the vaccine. 44,46 Therefore, we have proposed these as predictive biomarkers of optimal vaccine-induced antibody responses. 44,46 Polymerase chain reaction (PCR)-based spectratyping analyses of the lengths of the complementarity determining region (CDR)3, used to assess repertoire diversity, have shown agerelated changes in the relative proportions of large clonal populations of both T cells and B cells (reviewed in 88 ).…”

“…44,46 Therefore, we have proposed these as predictive biomarkers of optimal vaccine-induced antibody responses. 44,46 Polymerase chain reaction (PCR)-based spectratyping analyses of the lengths of the complementarity determining region (CDR)3, used to assess repertoire diversity, have shown agerelated changes in the relative proportions of large clonal populations of both T cells and B cells (reviewed in 88 ). In particular, it was shown that a significant proportion of elderly individuals have a dramatic collapse in their B cell repertoire diversity and that the extent of loss in B cell diversity correlates with their health status.…”