Polysaccharide Conjugate Vaccine against Pneumococcal Pneumonia in Adults

Abstract

BACKGROUNDPneumococcal polysaccharide conjugate vaccines prevent pneumococcal disease in infants, but their efficacy against pneumococcal community-acquired pneumonia in adults 65 years of age or older is unknown. METHODSIn a randomized, double-blind, placebo-controlled trial involving 84,496 adults 65 years of age or older, we evaluated the efficacy of 13-valent polysaccharide conjugate vaccine (PCV13) in preventing first episodes of vaccine-type strains of pneumococcal community-acquired pneumonia, nonbacteremic and noninvasive pneumococcal community-acquired pneumonia, and invasive pneumococcal disease. Standard laboratory methods and a serotype-specific urinary antigen detection assay were used to identify community-acquired pneumonia and invasive pneumococcal disease. RESULTSIn the per-protocol analysis of first episodes of infections due to vaccine-type strains, community-acquired pneumonia occurred in 49 persons in the PCV13 group and 90 persons in the placebo group (vaccine efficacy, 45.6%; 95.2% confidence interval [CI], 21.8 to 62.5), nonbacteremic and noninvasive community-acquired pneumonia occurred in 33 persons in the PCV13 group and 60 persons in the placebo group (vaccine efficacy, 45.0%; 95.2% CI, 14.2 to 65.3), and invasive pneumococcal disease occurred in 7 persons in the PCV13 group and 28 persons in the placebo group (vaccine efficacy, 75.0%; 95% CI, 41.4 to 90.8). Efficacy persisted throughout the trial (mean follow-up, 3.97 years). In the modified intention-totreat analysis, similar efficacy was observed (vaccine efficacy, 37.7%, 41.1%, and 75.8%, respectively), and community-acquired pneumonia occurred in 747 persons in the PCV13 group and 787 persons in placebo group (vaccine efficacy, 5.1%; 95% CI, −5.1 to 14.2). Numbers of serious adverse events and deaths were similar in the two groups, but there were more local reactions in the PCV13 group. CONCLUSIONSAmong older adults, PCV13 was effective in preventing vaccine-type pneumococcal, bacteremic, and nonbacteremic community-acquired pneumonia and vaccinetype invasive pneumococcal disease but not in preventing community-acquired pneumonia from any cause. (Funded by Pfizer; CAPITA ClinicalTrials.gov number NCT00744263.)

Current status and future directions of invasive pneumococcal diseases and prophylactic approaches to control them

“…5 This vaccine showed evidence of protection against invasive disease in adults. 12 , 15 There is also some evidence to suggest the vaccine protects the elderly, which is a high-risk population for pneumococcal infections. 16 However, the vaccine still has many shortcomings, including poor immunogenicity in children, especially those under the age of two.…”

“…16 However, the vaccine still has many shortcomings, including poor immunogenicity in children, especially those under the age of two. 15 There is also no strong evidence showing protection in immunocompromised patients. 5 The effectiveness of PPSV23 seems to decrease with age of the patient and time since administration.…”

“…Much like PCV7, PCV13 contains the CPS of 13 virulent serotypes conjugated to CRM197 (Table 1). 15 PCV13 showed promising results for protecting against invasive pneumonia infection as well as otitis media in young children. 5 Additionally, a 2015 study on PCV13 found it to be protective against CAP in elderly patients.…”

“…The introduction of PCV7 saw a great reduction in pneumococcal pneumonia cases in children; however, its impact on adult disease was not well studied. 5 , 15 With the introduction of PCV13, a greater impact of protection was observed in adults, specifically 65 and older. 15 …”

Assessing the function of pneumococcal neuraminidases NanA, NanB and NanC inin vitroandin vivolung infection models using monoclonal antibodies

“…However, variable impacts of vaccination on invasive pneumococcal disease rates, such as bacteraemia, septicaemia or meningitis often combined with pneumonia, have been reported in the elderly [3,4]. Rates of non-bacteraemic pneumococcal pneumonia in this age group have remained largely unaffected [5–7]. Present challenges in combating S. pneumoniae infections include serotype replacement (i.e.…”