A longitudinal analysis of pneumococcal vaccine serotypes in pneumonia patients in Germany

Recently, a 15-valent (PCV15) and a 20-valent pneumococcal conjugate vaccine (PCV20) have been licensed by the US Food and Drug Administration and are under evaluation by the European Medicines Agency. PCV15 contains all serotypes of the 13-valent conjugate vaccine (PCV13) plus serotype 22F and 33F and PCV20 includes PCV13 serotypes plus serotypes 8, 10A, 11A, 12F, 15B, 22F, 33F. We investigated pneumococcal serotype distribution, secular trends and proportion of pneumonia caused by serotypes included in PCV13, PCV15, PCV20, and the 23-valent pneumococcal polysaccharide vaccine (PPV23) among adult patients with all-cause community-acquired pneumonia (CAP) between 2013 and 2019. We applied logistic mixed regression modelling to assess annual trends. Urine samples from adult patients with CAP treated in the community or hospital in Germany and included in the CAPNETZ study, a prospective multi-centre cohort study, were analysed by two serotype-specific multiplex urinary antigen detection assays (UAD1/UAD2) at Pfizer’s Vaccines Research and Development Laboratory. UAD1 detects serotypes in PCV13, UAD2 detects additional serotypes in PCV20 plus serotypes 2, 9N, 17F and 20. Out of 1,831 patients screened, urine samples with a valid UAD test result were available for 1,343 patients (73.3%). Among those patients, 829 patients (61.7%) were male, 792 patients (59.0%) were aged ≥60 years, 1038 patients (77.3%) had at least one comorbidity and 1,204 patients (89.7%) were treated in the hospital. The overall proportion of vaccine-type pneumonia among all-cause CAP for PCV13, PCV15, PCV20 and PPV23 was 7.7% (n=103), 9.1% (n=122), 12.3% (n=165) and 13.3% (n=178). Over the entire observation period, we did not observe evidence for significant annual trends in pneumococcal vaccine serotype coverage against pneumonia in adults (PCV13: OR 0.94, 95% CI 0.83-1.05; PCV15: OR 0.93, 95% CI 0.84-1.03; PCV20: OR 0.95, 95% CI 0.86-1.04; PPV23: OR 0.99, 95% CI 0.90-1.08). In conclusion, our data show i) no decline of PCV13 serotypes in all-cause CAP between 2013-2019 mainly due to a persistently high proportion of serotype 3 suggesting no meaningful effect of childhood PCV13 vaccination on PCV13 coverage in pneumonia in adults during this time period and ii) that the gap in the coverage between PCV20 and PPV23 was small and did not increase over the entire observation time. ### Competing Interest Statement CB is a member of the scientific advisory board of GSK and reports personal fees from Pfizer for lectures and travel, all outside the submitted work. MK reports personal fees from Berlin Chemie, Boehringer, Astrazeneca, Biotest, Novartis, GSK, Gilead, Pfizer and MSD and a research grant from Pfizer outside the submitted work. SE is a member of the scientific advisory board of Pfizer. GR reports personal fees from Astrazeneca, Berlin Chemie, BMS, Pfizer, Boehringer Ingelheim, Solvay, Insmed, GSK, Essex Pharma, MSD, Grifols, Chiesi, Vertex, Roche, Takeda and Novartis for lectures including service on speakers' bureau outside the submitted work and/or consultancy during advisory board meedings and personal fees from GSK for travel accommodations/meeting expenses, outside the submitted work. As part of her activity as a member of the executive bodies, GB-N reports economic connections to the following diagnostic and pharmaceutical companies: ThermoFisher Scientific / BRAHMS, Alere Technologies GmbH, Merck Sharp and Dohme Corp., Pfizer Pharma GmbH, R-Biopharm AG and Helmut Hund GmbH. MW received personal fees from Astrazeneca, Bayer Health Care, Berlin Chemie, Biotest, Chiesi, Novartis, Teva, and research funding from Actelion, Bayer Health Care, Biotest, Boehringer Ingelheim, all unrelated to the current work. TW is the head of clinical studies and a member of the speakers' bureau for Pfizer, Bio Merieux and Roche Diagnostics and is a consultant to Pfizer and MSD. MWP is a consultant to and a member of the speakers' bureau for Bayer, MSD, Pfizer, meduptodate, Thermofisher and Novartis and has received research grants from Pfizer. JR and MKe have declared no conflict of interest. ### Funding Statement CAPNETZ was founded by a German Federal Ministry of Education and Research grant (01KI07145) 2001-2011. Since 2013 CAPNETZ was supported by the German Center for Lung Research (DZL): 2013-2015 Funding code 82DZL00204 and 2016-2020 Funding code 82DZL002A4. CB and MWP are partly supported by a grant of the Federal Ministry of Education and Research KliFo 2.0 (grant number 01KI1501). MW is supported by grants from the German Research Foundation, SFB-TR84 C6 and C9, SFB 1449 B2, by the German Ministry of Education and Research (BMBF) in the framework of the CAPSyS (01ZX1304B), CAPSyS-COVID (01ZX1604B), SYMPATH (01ZX1906A), PROVID (01KI20160A) P4C (16GW0141), MAPVAP (16GW0247), NUM-NAPKON (01KX2021), and by the Berlin Institute of Health (CM-COVID). This study was supported by an unrestricted grant from Pfizer. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The Ethics Committee Medical Faculty of Otto-von-Guericke-University Magdeburg gave ethical approval for this work I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors * CAP : community-acquired pneumonia CI : confidence interval OR : odds ratio PCV7 : 7-valent conjugate vaccine PCV10 : 10-valent conjugate vaccine PCV13 : 13-valent conjugate vaccine PCV15 : 15-valent conjugate vaccine PCV20 : 20-valent conjugate vaccine PPV23 : 23-valent pneumococcal polysaccharide vaccine STIKO : German Standing Committee on Immunization UAD : serotype-specific multiplex urinary antigen detection assay