Burden of lower respiratory tract infections preventable by adult immunization with 15- and 20-valent pneumococcal conjugate vaccines in the United States

Background Updated 2022 recommendations indicate all US adults aged ≥65 years and adults aged <65 years with comorbid conditions should receive 15- and 20-valent pneumococcal conjugate vaccines (PCV15/20). We aimed to assess the potential impact of these recommendations on the burden of lower respiratory tract infections (LRTIs) among adults. Methods We estimated the incidence of LRTI cases and associated hospital admissions among enrollees of Kaiser Permanente Southern California health plans from 2016-19. We used a counterfactual inference framework to estimate excess LRTI-associated risk of death up to 180 days after diagnosis. We used prior estimates of PCV13 effectiveness against all-cause and serotype-specific LRTI to model potential direct effects of PCV15/20 by age group and risk status. Results Use of PCV15 and PCV20, respectively, could prevent 89.3 (95% confidence interval: 41.3-131.8) and 108.6 (50.4-159.1) medically-attended LRTI cases per 10,000 person-years; 21.9 (10.1-32.0) and 26.6 (12.4-38.7) hospitalized LRTI cases per 10,000 person-years; and 7.1 (3.3-10.5) and 8.7 (4.0-12.7) excess LRTI-associated deaths per 10,000 person-years. Among at-risk adults aged <65 years not previously prioritized for receipt of PCV13, PCV15 and PCV20, respectively, could prevent 85.7 (39.6-131.5) and 102.7 (47.8-156.7) medically-attended LRTI cases per 10,000 person-years; 5.1 (2.4-8.6) and 6.2 (2.8-10.2) LRTI hospitalizations per 10,000 person-years, and 0.9 (0.4-1.4) and 1.1 (0.5-1.7) excess LRTI-associated deaths per 10,000 person-years. Expansions in serotype coverage, relative to PCV13, accounted for the majority of the expected increase in vaccine-preventable hospitalizations and deaths. Conclusions Our findings suggest recent recommendations including PCV15/20 within adult pneumococcal vaccine series may substantially reduce LRTI burden. Key points ### Competing Interest Statement JAL discloses receipt of grant funding and consulting fees from Pfizer and from Merck, Sharp & Dohme, unrelated to this study. KJB discloses receipt of grant funding from Dynavax, Gilead, GlaxoSmithKline, and Moderna, unrelated to this study. SYT discloses receipt of grant funding from Pfizer for this study and for unrelated projects. LRG, AC, LJ, AA, and BDG are employees of Pfizer. ### Funding Statement The study was funded by Pfizer, Inc. ### 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 study was reviewed and approved by the Kaiser Permanente Southern California Institutional Review Board. 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 Anonymized data that support the findings of this study may be made available from the investigative team in the following conditions: (1) agreement to collaborate with the study team on all publications, (2) provision of external funding for administrative and investigator time necessary for this collaboration, (3) demonstration that the external investigative team is qualified and has documented evidence of training for human subjects protections, and (4) agreement to abide by the terms outlined in data use agreements between institutions.