23-Valent Pneumococcal Polysaccharide Vaccination Does Not Prevent Community-Acquired Pneumonia Hospitalizations Due to Vaccine-Type Streptococcus pneumoniae

Chandler, Thomas; Furmanek, Stephen; Carrico, Ruth; Balcom, Dawn; Arnold, Forest W.; Ramírez, Julio

doi:10.3390/microorganisms10030560

Cited by 23 publications

(21 citation statements)

References 15 publications

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“…PCV7, PCV10, and PCV13 have demonstrated robust protection against invasive and noninvasive disease including pneumonia, acute otitis media, and nasopharyngeal carriage among children; further, PCV13 protected against adult vaccine-type invasive disease and bacteremic and nonbacteremic pneumonia in an RCT in The Netherlands (10)(11)(12)(13). Although no RCT has directly compared the efficacy of PCV vaccines with that of PPSV23 in adult populations, one study in Louisville, KY, among persons aged 65 or older reported vaccine effectiveness of 71% for PCV13 against vaccine-type pneumonia (14), whereas a second study reported effectiveness of 17% for PPSV23 against pneumonia for PPSV23-unique serotypes (15). Similar paired data from Germany and the United States reported effectiveness against all-cause pneumonia in older adults of 12 and 8.8% for PCV13 compared with 3 and 1% for PPSV23 (16)(17)(18).…”

Section: Introductionmentioning

confidence: 99%

Polysaccharide and conjugate vaccines to Streptococcus pneumoniae generate distinct humoral responses

et al. 2022

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Streptococcus pneumoniae is a major cause of community-acquired pneumonia, bacteremia, and meningitis in older adults worldwide. Two pneumococcal vaccines containing S. pneumoniae capsular polysaccharides are in current use: the polysaccharide vaccine PPSV23 and the glycoconjugate vaccine PCV13. In clinical trials, both vaccines elicit similar opsonophagocytic killing activity. In contrast to polysaccharide vaccines, conjugate vaccines have shown consistent efficacy against nasopharyngeal carriage and noninvasive pneumonia overall and for some prevalent individual serotypes. Given these different clinical profiles, it is crucial to understand the differential immunological responses induced by these two vaccines. Here, we used a high-throughput systems serology approach to profile the biophysical and functional features of serum antibodies induced by PCV13 and PPSV23 at 1 month and 1 year. In comparison with PPSV23, PCV13 induced higher titers across antibody isotypes; more durable antibody responses across immunoglobulin G (IgG), IgA, and IgM isotypes; and increased antigenic breadth. Although titers measured in opsonophagocytic activity (OPA) assays were similar between the two groups, confirming what was observed in clinical studies, serum samples from PCV13 vaccinees could induce additional non-OPA antibody-dependent functions, including monocyte phagocytosis and natural killer cell activation. In a multivariate modeling approach, distinct humoral profiles were demonstrated in each arm. Together, these results demonstrate that the glycoconjugate PCV13 vaccine induces an antigenically broader, more durable, polyfunctional antibody response. These findings may help explain the increased protection against S. pneumoniae colonization and noninvasive pneumonia and the longer duration of protection against invasive pneumococcal disease, mediated by PCV13.

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Section: Introductionmentioning

confidence: 99%

Polysaccharide and conjugate vaccines to Streptococcus pneumoniae generate distinct humoral responses

et al. 2022

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“…Lastly, PCV13 (pneumococcal conjugate vaccine) vaccination is recommended for infants 2 months to 2 years old, and those with immunosuppressive diseases under the age of 19 are also recommended to be vaccinated [ 32 ]. Adults above 65 years of age are recommended PPSV23 (Pneumococcal Polysaccharide Vaccine) to prevent themselves from acquiring CABP [ 33 ]. A major concern related to the treatment of patients with CABP include adverse effects as well as collateral damage to the microbiome with an associated risk of Clostridium difcile infection [ 34 , 35 ].…”

Section: Current Strategiesmentioning

confidence: 99%

Lefamulin: a New Hope in the Field of Community-Acquired Bacterial Pneumonia

et al. 2022

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Purpose of Review Community-acquired bacterial pneumonia (CABP) continues to be a worldwide health concern since it is the major cause of mortality and hospitalisation worldwide. Increased macrolide resistance among Streptococcus pneumoniae and other infections has resulted in a significantly larger illness burden, which has been exacerbated by evolving demography and a higher prevalence of comorbid disorders. Owing to such circumstances, the creation of new antibiotic classes is critical. Recent Findings Lefamulin, also referred to as BC-3781, is the primary pleuromutilin antibiotic which has been permitted for both intravenous and oral use in humans for the remedy of bacterial infections. It has shown activity against gram-positive bacteria including methicillin-resistant strains as well as atypical organisms which as often implicated in CABP. It has a completely unique mechanism of action that inhibits protein synthesis via way of means of stopping the binding of tRNA for peptide transfer. The C(14) side chain is responsible for its pharmacodynamic and antimicrobial properties, together with supporting in overcoming bacterial ribosomal resistance and mutations improvement amplifying the number of hydrogen bonds to the target site. Summary This review aims to highlight the pre-existing treatment options and specific purposes to shed some light upon the development of a new drug lefamulin and its specifications and explore this novel drug’s superior efficacy to already existing treatment strategies.

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“…18 Systematic reviews and meta-analyses support the efficacy of PPV23 against invasive pneumococcal disease (IPD); however, VE against non-bacteraemic pneumococcal pneumonia is uncertain. [19][20][21][22][23] The current consensus is that PPV23 does not offer protection against natural colonisation. 19 Effects in CHIMs have yet to be established.…”

Section: Pneumococcal Vaccinesmentioning

confidence: 99%

“…To compare the rate of acquisition of experimental SPN6B colonisation at EACH and ANY time point during the23 days following EHPC in persons 6 months post pneumococcal vaccination (PCV-13 or PPV-23) to controls defined by classical culture and molecular methods from NW. The rate of experimental SPN6B colonisation determined by the presence of experimental SPN6B in NW by classical culture and PCR (combined and individually) at EACH and ANY time point (D2, 7, 14, 23) following EHPC 6 months after vaccination in PCV-13 vs control and PPV-23 vs control.…”

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confidence: 99%

Protocol for a phase IV double-blind randomised controlled trial to investigate the effect of the 13-valent pneumococcal conjugate vaccine and the 23-valent pneumococcal polysaccharide vaccine on pneumococcal colonisation using the experimental human pneumococcal challenge model in healthy adults (PREVENTING PNEUMO 2)

et al. 2022

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IntroductionDespite widely available vaccinations, Streptococcus pneumoniae (SPN) remains a major cause of morbidity and mortality worldwide, causing community-acquired pneumonia, meningitis, otitis media, sinusitis and bacteraemia. Here, we summarise an ethically approved protocol for a double-blind, randomised controlled trial investigating the effect of the 13-valent pneumococcal conjugate vaccine (PCV13) and the 23-valent pneumococcal polysaccharide vaccine (PPV23) on pneumococcal nasopharyngeal colonisation acquisition, density and duration using experimental human pneumococcal challenge (EHPC).Methods and analysisHealthy adult participants aged 18–50 years will be randomised to receive PCV13, PPV23 or placebo and then undergo one or two EHPCs involving intranasal administration of SPN at 1-month post-vaccination with serotype 3 (SPN3) and 6 months with serotype 6B (SPN6B). Participants randomised to PCV13 and placebo will also be randomised to one of two clinically relevant SPN3 strains from distinct lineages within clonal complex 180, clades Ia and II, creating five study groups. Following inoculation, participants will be seen on days 2, 7, 14 and 23. During the follow-up period, we will monitor safety, colonisation status, density and duration, immune responses and antigenuria. The primary outcome of the study is comparing the rate of SPN3 acquisition between the vaccinated (PCV13 or PPV23) and unvaccinated (placebo) groups as defined by classical culture. Density and duration of colonisation, comparison of acquisition rates using molecular methods and evaluation of the above measurements for individual SPN3 clades and SPN6B form the secondary objectives. Furthermore, we will explore the immune responses associated with these vaccines, their effect on colonisation and the relationship between colonisation and urinary pneumococcal antigen detection.Ethics and disseminationThe study is approved by the NHS Research and Ethics Committee (Reference: 20/NW/0097) and by the Medicines and Healthcare products Regulatory Agency (Reference: CTA 25753/0001/001–0001). Findings will be published in peer-reviewed journals.Trial registration numberISRCTN15728847, NCT04974294.

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23-Valent Pneumococcal Polysaccharide Vaccination Does Not Prevent Community-Acquired Pneumonia Hospitalizations Due to Vaccine-Type Streptococcus pneumoniae

Cited by 23 publications

References 15 publications

Polysaccharide and conjugate vaccines to Streptococcus pneumoniae generate distinct humoral responses

Polysaccharide and conjugate vaccines to Streptococcus pneumoniae generate distinct humoral responses

Lefamulin: a New Hope in the Field of Community-Acquired Bacterial Pneumonia

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