Efficacy of pneumococcal vaccination in adults: a meta-analysis

Abstract

Background: Clinical trials and meta-analyses have produced conflicting results of the efficacy of unconjugated pneumococcal polysaccharide vaccine in adults. We sought to evaluate the vaccine's efficacy on clinical outcomes as well as the methodologic quality of the trials. Methods:We searched several databases and all bibliographies of reviews and meta-analyses for clinical trials that compared pneumococcal polysaccharide vaccine with a control. We examined rates of pneumonia and death, taking the methodologic quality of the trials into consideration. Results:We included 22 trials involving 101 507 participants: 11 trials reported on presumptive pneumococcal pneumonia, 19 on all-cause pneumonia and 12 on allcause mortality. The current 23-valent vaccine was used in 8 trials. The relative risk (RR) was 0.64 (95% confidence interval [CI] 0.43-0.96) for presumptive pneumococcal pneumonia and 0.73 (95% CI 0.56-0.94) for all-cause pneumonia. There was significant heterogeneity between the trials reporting on presumptive pneumonia (I 2 = 74%, p < 0.001) and between those reporting on all-cause pneumonia (I 2 = 90%, p < 0.001). The RR for all-cause mortality was 0.97 (95% CI 0.87-1.09), with moderate heterogeneity between trials (I 2 = 44%, p = 0.053). Trial quality, especially regarding double blinding, explained a substantial proportion of the heterogeneity in the trials reporting on presumptive pneumonia and all-cause pneumonia. There was little evidence of vaccine protection in trials of higher methodologic quality (RR 1.20, 95% CI 0.75-1.92, for presumptive pneumonia; and 1.19, 95% CI 0.95-1.49, for allcause pneumonia in double-blind trials; p for heterogeneity > 0.05). The results for all-cause mortality in double-blind trials were similar to those in all trials combined. There was little evidence of vaccine protection among elderly patients or adults with chronic illness in analyses of all trials (RR 1.04, 95% CI 0.78-1.38, for presumptive pneumococcal pneumonia; 0.89, 95% CI 0.69-1.14, for all-cause pneumonia; and 1.00, 95% CI 0.87-1.14, for all-cause mortality).Interpretation: Pneumococcal vaccination does not appear to be effective in preventing pneumonia, even in populations for whom the vaccine is currently recommended.

Background paper to the updated pneumococcal vaccination recommendation for older adults in Germany

“…1. The results of the previously published meta-analyses by Moberley et al [36] and Huss et al [61] were greatly influenced by the trials by Honkanen et al [41] and Örtqvist et al [40]. We included these two trials for the endpoint IPD, but not for the endpoint PP because in a large number of cases in both studies, the PP diagnosis was based on detection of pneumolysin IgG in serum [54] or in circulating immune complexes in serum [55], using poorly validated inhouse ELISAs.…”

“…At the time of our own literature searches, the Cochrane review by Moberley et al [36] and a review by Huss et al [61] were the most recent ones. Because different studies were included or excluded, the findings of those two reviews are contradictory in some points; see also the correspondence between the authors [62,63].…”

“…It is often claimed that the protection offered by the pure (non-conjugate) polysaccharide vaccine against PP has not been proved (e. g. [22,61]). However, the current Cochrane review from 2013 [36] shows a pooled efficacy of 28 % (95 % CI, 7-44 %) against all-cause pneumonia.…”

Polysaccharide-specific B cell responses to vaccination in humans

“…This vaccine appears to offer a degree of short-term protection against invasive pneumococcal disease, 35 but no reduction in rates of pneumonia or mortality. 36,37 Furthermore, immunization with plain polysaccharide vaccines may reduce antibody levels induced by prior receipt of a polysaccharide-containing vaccine, an effect known as hyporesponsiveness. This phenomenon has been demonstrated in children 38 and more recently in adults, 39 although another smaller adult study did not identify an effect.…”

Polysaccharide Conjugate Vaccine against Pneumococcal Pneumonia in Adults

“…36 Most earlier randomized studies of vaccination with either free polysaccharide vaccines in older adults 37 or pneumococcal conjugate vaccines in HIV-infected adults 21 were underpowered to show efficacy against vaccinetype community-acquired pneumonia; results of these studies and other observational studies have been inconsistent. [11][12][13][14] Our study had several limitations. The study was performed in a single country in a homogeneous population of participants among whom there was a low incidence of pneumococcal disease.…”