# Randomized Phase 3 Trial Evaluating the Safety, Tolerability, and Immunogenicity of V114, a 15-Valent PCV, Followed by PPSV23 6 Months Later (PNEU-DAY): Subgroup Analysis in Adults 18–49 Years of Age Enrolled at Center for Indigenous Health Sites

## TL;DR

A new 15-valent pneumococcal vaccine, V114, was tested in American Indian adults and found to be safe and effective, offering broader protection than existing vaccines.

## Contribution

The study demonstrates the immunogenicity and safety of V114 in a high-risk population, offering expanded serotype coverage compared to PCV13.

## Key findings

- V114 induced robust immune responses to two additional serotypes (22F and 33F) not included in PCV13.
- Sequential administration of V114 followed by PPSV23 was immunogenic and well tolerated.
- Nasopharyngeal/oropharyngeal carriage of S. pneumoniae was observed in 16.7% to 22.6% of participants.

## Abstract

Background/Objectives: American Indian/Alaska Native individuals exhibit a higher prevalence of carriage of Streptococcus pneumoniae and are at increased risk of invasive pneumococcal disease compared with the general US population, driven by persistent inequities in health determinants. Although the use of pneumococcal vaccines has reduced carriage of vaccine serotypes, the prevalence of carriage of non-vaccine serotypes has increased. Methods: This study was a descriptive subgroup analysis of the PNEU-DAY study (NCT03547167; EudraCT 2017-004915-38). Safety, tolerability, and immunogenicity of sequential administration of either V114, a 15-valent pneumococcal conjugate vaccine (PCV), or 13-valent PCV (PCV13), followed 6 months later by 23-valent pneumococcal polysaccharide vaccine (PPSV23), were evaluated in pneumococcal vaccine-naïve American Indian adults with or without pre-defined risk factors for pneumococcal disease. Polymerase chain reaction testing assessed nasopharyngeal/oropharyngeal carriage of S. pneumoniae. Results: Following administration of PCV and PPSV23, the proportions of participants with adverse events were generally comparable between vaccination groups. V114 and PCV13 were immunogenic for all respective vaccine serotypes, with V114 inducing robust immune responses to the two additional serotypes not included in PCV13 (22F and 33F), based on opsonophagocytic activity geometric mean titers and immunoglobulin G geometric mean concentrations at 30 days post-vaccination. Sequential administration with PPSV23 was immunogenic in both vaccination groups. Nasopharyngeal/oropharyngeal carriage of S. pneumoniae was observed in 16.7% to 22.6% of American Indian participants across the study timepoints. Conclusions: V114 was well tolerated and immunogenic for the 15 serotypes in V114 when administered either alone or followed by PPSV23. Use of V114 has the potential to expand serotype coverage and protect against pneumococcal disease resulting from serotypes absent in PCV13 among American Indian adults.