Pneumococcal conjugate vaccine herd effects on non-invasive pneumococcal pneumonia in elderly

Werkhoven, Cornelis H. van; Hollingsworth, Rosalind; Huijts, Susanne M.; Bolkenbaas, Marieke; Webber, Chris; Patterson, Scott D.; Sanders, Elisabeth A. M.; Bonten, Marc J. M.

doi:10.1016/j.vaccine.2016.05.002

Cited by 30 publications

(25 citation statements)

References 28 publications

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“…[1][2][3][4] However, infection and nasopharyngeal colonization by non-vaccine serotypes and nonencapsulated Streptococcus pneumoniae (NESp) have increased worldwide. 4,5 Although NESp strains are generally considered less virulent than encapsulated strains, [6][7][8][9] NESp strains have been repeatedly isolated from patients with various pneumococcal diseases, including conjunctivitis, acute otitis media (AOM), acute rhinosinusitis, and systemic infections (albeit rarely, and mostly in immunocompromised patients).…”

Section: Introductionmentioning

confidence: 99%

Molecular characterization of pneumococcal surface protein K, a potential pneumococcal vaccine antigen

et al. 2017

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The pneumococcal capsule is indispensable for pathogenesis in systemic infections; however, many pneumococcal diseases, including conjunctivitis, otitis media, and some systemic infections in immunocompromised patients, are caused by nonencapsulated Streptococcus pneumoniae (NESp). Null capsule clade 1 (NCC1), found in group 2 NESp, expresses pneumococcal surface protein K (PspK) and is becoming prevalent among pneumococcal organisms owing to the widespread use of pneumococcal conjugate vaccines. Despite its clinical importance, the molecular mechanisms underlying the prevalence of NCC1 have not been fully elucidated. Here, we investigated the role of the R3 domain of PspK in the epithelial cell adherence of NCC1. We found that the R3 domain of PspK mediated NCC1 adherence via its direct interaction with the epithelial surface protein annexin A2. Additionally, neutralization with purified recombinant PspK-R3 or rabbit anti-UD:R3 IgG inhibited binding of NESp to lung epithelial cells in vitro. Immunization with the 'repeat' domain of PspK-R3 or PspK-UD:R3 effectively elicited mucosal and systemic immune responses against PspK-R3 and provided protection against nasopharyngeal, lung, and middle ear colonization of NESp in mice. Additionally, we found that rabbit anti-UD:R3 IgG bound to PspC-R1 of the encapsulated TIGR4 strain and that UD:R3 immunization provided protection against nasopharyngeal and lung colonization of TIGR4 and deaths by TIGR4 and D39 in mice. Further studies using 68 pneumococcal clinical isolates showed that 79% of clinical isolates showed cross-reactivity to rabbit anti-UD:R3 IgG. About 87% of serotypes in the 13-valent pneumococcal conjugate vaccine (PCV) and 68% of nonvaccine serotypes were positive for cross-reactivity with rabbit anti-UD:R3 IgG. Thus, the R3 domain of PspK may be an effective vaccine candidate for both NESp and encapsulated Sp.

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Section: Introductionmentioning

confidence: 99%

Molecular characterization of pneumococcal surface protein K, a potential pneumococcal vaccine antigen

et al. 2017

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“…The same happened with the majority of those included in the CAP2 period, as PCV13 vaccine was approved for use in adults in 2012, and only indicated in adults older than 65 years-old by the CoNain in 2016, after the CAPiTA study was published. The CAPITA study demonstrated among this population that PCV13 was effective in preventing vaccine-type pneumococcal, bacteremic, and nonbacteremic CAP and vaccine type invasive pneumococcal disease, but not in preventing community-acquired pneumonia from any cause [ 14 , 20 ].…”

Section: Resultsmentioning

confidence: 99%

Decreased relative risk of pneumococcal pneumonia during the last decade, a nested case-control study

et al. 2018

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BackgroundStreptococcus pneumoniae (SP) is one of the most common pathogens of Community-Acquired Pneumonia (CAP), but recent reports suggest that its incidence may be declining in relation to the use of the conjugate 13-valent pneumococcal vaccine in children. We compared the result of the immunochromatographic SP urinary antigen test (SPUAT) and clinical outcomes in patients with CAP admitted in two periods of time: 2001–2002(CAP1) and 2015–2016(CAP2).MethodsThis was a matched nested case-control study of two prospectively recorded cohorts of patients admitted with CAP, with SPUAT and blood culture performed in all patients. CAP2 cases and CAP1 controls were matched for age ± 4 years, sex, and Pneumonia Severity Index (PSI) score ± 10 points. Odds ratios (OR) for having SPUAT positive was estimated by conditional logistic regression. A multivariate model assessed the contribution of individual variables.ResultsFour hundred ninety-eight patients were recruited; 307 during the CAP1 and 191 during the CAP2 periods. Comparing both periods we observed differences, in age, PSI score, and the percentage of smokers, outpatients, previously immunized with pneumococcal vaccine, and positive SPUAT. On the other hand, mortality, admission from nursing homes, pneumococcal bacteremia and hospital admission were not different. After matching, pneumonia due to SP per the SPUAT was observed in 34(23.4%) of CAP1 and in 12(8.3%) of CAP2 patients (p < 0.001), and 6/145 CAP1 vs 33/145 CAP2 patients had received pneumococcal immunization before their admission (p < 0.001). A multivariate analysis confirmed that, independent of falling into PSI class 5, having not received the pneumococcal vaccine and having not survived the episode of pneumonia, there were two factors that increased the probability of having SPUAT positive: developing pneumonia during the CAP1 period (OR = 1.23) and having pneumococcal bacteremia (OR = 2.66).ConclusionWe observed a reduction of the role of SP as pathogen, along with an increase in the number of patients who received pneumococcal immunization before admission, in 2015-2016 compared to 2001-2002. In addition, the use of conjugate 13-valent vaccine, starting in 2012 for childhood immunization, could be an additional factor contributing to these changes, as a result of early herd immunity in adults pneumonia.

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“…This analysis found that PCV7 serotypes decreased from 28% to 7%. There was no reduction in the additional PCV10 and PCV13 serotypes, and non-PCV13 serotypes increased from 30% to 37% [62]. While these findings support concordant trends in indirect protection from both PCV7 CAP and IPD among the elderly adult population, they also suggest a similar trend in serotype replacement for pneumococcal CAP and IPD.…”

Section: Effects Of Vaccination On Pneumococcal Diseasesmentioning

confidence: 95%

Indirect Effects of Pneumococcal Conjugate Vaccines in National Immunization Programs for Children on Adult Pneumococcal Disease

2016

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The pneumococcal conjugate vaccine (PCV) was developed to overcome the limitations of the pneumococcal polysaccharide vaccine, which produces poor immunogenicity in infants younger than 2 years. As many countries have included PCVs in national immunization programs for children, the incidence of invasive pneumococcal disease caused by vaccine type Streptococcus pneumoniae has declined markedly, not only among the vaccinated pediatric population, but also among unvaccinated adults. In this review, we present a concise overview of the indirect effects of mass pediatric PCV immunization on unvaccinated adults.

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Pneumococcal conjugate vaccine herd effects on non-invasive pneumococcal pneumonia in elderly

Cited by 30 publications

References 28 publications

Molecular characterization of pneumococcal surface protein K, a potential pneumococcal vaccine antigen

Molecular characterization of pneumococcal surface protein K, a potential pneumococcal vaccine antigen

Decreased relative risk of pneumococcal pneumonia during the last decade, a nested case-control study

Indirect Effects of Pneumococcal Conjugate Vaccines in National Immunization Programs for Children on Adult Pneumococcal Disease

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