Cytomegalovirus serostatus, inflammation, and antibody response to influenza vaccination in older adults: The moderating effect of beta blockade

Abstract

Cytomegalovirus (CMV) has been implicated as a factor in immunosenescence, including poor antibody response to vaccination and higher immune activation and inflammation. Some people may be more or less vulnerable to the negative effects of CMV. The present investigation tested the effects of beta-blocker use and chronological age on the associations between CMV and immunity in adults aged 60–91 (N=98; 69% CMV seropositive) who were administered the trivalent influenza vaccine for up to 5 years. Peak antibody response, corrected for baseline, and spring (persistent) antibody response, corrected for peak, were assessed, as well as beta-2 microglobulin (β2μ) and interleukin-6 (IL-6). In multi-level models with years at Level 1 and people at Level 2, CMV serostatus did not predict peak antibody response, but there was a 3-way interaction between CMV serostatus, age, and beta-blockers. Age was negatively associated with peak antibody, but only among adults who were CMV seropositive and taking beta-blockers. CMV seronegative adults who were not taking beta-blockers had the highest antibody persistence. CMV serostatus was not associated with β2μ or IL-6. Results suggest that CMV+ serostatus may negatively compromise antibody response to a greater degree than inflammatory markers in older adults. Furthermore, older adults who take beta-blockers may be more vulnerable to negative effects of age and CMV on peak antibody response, perhaps by virtue of their underlying health condition.

Effect of latent cytomegalovirus infection on the antibody response to influenza vaccination: a systematic review and meta-analysis

“…The potential influence of latent CMV-infection on the antibody response to influenza vaccination was also investigated by extracting the association between the CMV antibody level and the influenza antibody titer. Five studies reported this outcome variable, either as a correlation between the CMV antibody level and the influenza antibody titer post-vaccination or using a regression model, in which additional factors than only CMV antibody level, such as age, were taken into account [25, 42, 47, 55, 56]. The five studies together reported 10 individual records (Supplementary figure 4) and included younger and older adults (18–97 years) and different influenza strains (Table 4).…”

“…Thus, post-vaccination titers as outcome will overestimate the vaccine antibody response and are, therefore, less meaningful. Linear regression analysis, as performed in some studies [42, 63], is the best method to correct for pre-vaccination titers [46], but this could not be analyzed on the basis of the extracted data of the studies included for this review. Thus, with the GMR, the best outcome available, no effect of CMV seropositivity on the influenza vaccine response is observed.…”

Negative Effect of Age, but Not of Latent Cytomegalovirus Infection on the Antibody Response to a Novel Influenza Vaccine Strain in Healthy Adults

“…A beneficial effect of latent CMV infection on the long-term persistence of protection after vaccination in adults has to our knowledge not been reported. Waning of protection is thought to be most significant in individuals above 65 years of age ( 45 ) and accelerated by latent CMV infection ( 46 ). Our results might suggest a positive effect of CMV infection in adults on the protection rate.…”

‘From immunosenescence to immune modulation’: a re-appraisal of the role of cytomegalovirus as major regulator of human immune function

“…Furthermore, a potential mechanism is apparent as the vascular system is a major battleground of viral infection and immunological control. The virus is tropic for endothelial cells (81) and indeed the large CMV-specific immune response within the vascular system is believed to represent 'immune surveillance' of the vascular bed (82)(83)(84). This association of CMV with cardiovascular disease may help to explain why some of the more recent epidemiological studies of CMV infection in older people have failed to replicate earlier studies.…”