Cytomegalovirus (CMV) seropositivity decreases B cell responses to the influenza vaccine

Abstract

Cytomegalovirus (CMV)-seropositivity has been shown to have a negative effect on influenza vaccine-specific antibody responses. In this paper we confirm and extend these results showing for the first time a negative association between CMV-seropositivity and B cell predictive biomarkers of optimal vaccine responses. These biomarkers are switched memory B cells and AID in CpG-stimulated B cell cultures measured before vaccination which positively correlate with the serum response to the influenza vaccine. We also found that CMV-seropositivity is associated with increased levels of B cell-intrinsic inflammation and these both correlate with lower B cell function. Finally, CMV-seropositivity is associated with decreased percentages of individuals responding to the vaccine in both young and elderly individuals.

How does cytomegalovirus factor into diseases of aging and vaccine responses, and by what mechanisms?

“…CMV also impairs B cell responses to the influenza vaccine, and a negative association between CMV seropositivity and the B cell predictive biomarkers of optimal vaccine responses has been reported (Frasca et al 2015). In this cohort, CMV seropositivity has also been associated with increased levels of systemic and B cell-intrinsic inflammation, suggesting an additional mechanism by which CMV downregulates the B cell antibody response.…”

“…Results on the effect of CMV seropositivity on influenza vaccine responses are controversial with most of the studies showing a negative effect of CMV (Derhovanessian et al 2013b(Derhovanessian et al , 2014Frasca et al 2015;Trzonkowski et al 2003) and others showing no effect (den Elzen et al 2011;Furman et al 2015). The negative effects of CMV seropositivity have been associated in both elderly (Derhovanessian et al 2013b;Frasca et al 2015) and young (Frasca et al 2015) individuals with the presence of late differentiated/exhausted T cells (CD27 −CD28−CCR7−CD45RA+ or with CD28−CD57+), which produce pro-inflammatory cytokines and have therefore a significant role in age-related immune pathologies, suggesting that this virus may underlie rudimentary aspects of immunosenescence even in chronologically young individuals (Turner et al 2014).…”

“…The negative effects of CMV seropositivity have been associated in both elderly (Derhovanessian et al 2013b;Frasca et al 2015) and young (Frasca et al 2015) individuals with the presence of late differentiated/exhausted T cells (CD27 −CD28−CCR7−CD45RA+ or with CD28−CD57+), which produce pro-inflammatory cytokines and have therefore a significant role in age-related immune pathologies, suggesting that this virus may underlie rudimentary aspects of immunosenescence even in chronologically young individuals (Turner et al 2014). Results from a recently published study have demonstrated that CMV seropositivity negatively affects antibody response to the influenza vaccine to a greater extent than inflammatory markers, such as β2-microglobulin and IL-6, in older adults (Reed et al 2017).…”

Aging, cytomegalovirus (CMV) and influenza vaccine responses

“…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.…”

“…CMV has been associated with poor humoral response to influenza vaccination in the elderly 58,105 as well as the young 78 and with the presence of CD27-CD28-CCR7-CD45RAC or with CD28-CD57C T cells, both identified as late differentiated/exhausted T cells which produce pro-inflammatory cytokines and have therefore a significant role in age-related immune pathologies. 58,105 Also in young individuals, CMV has been associated with the induction of CD27-CD28-CD45RAC T cells and consequent suboptimal influenza vaccine responses, suggesting that this virus may underlie rudimentary aspects of immunosenescence even in chronologically young individuals.…”