Safety, reactogenicity, and immunogenicity of a novel 24-valent pneumococcal vaccine candidate in healthy, pneumococcal vaccine-naïve Japanese adults: A phase 1 randomized dose-escalation trial

Abstract

Background

The burden of pneumococcal diseases remains high in Japan. Pn-MAPS24v is a novel MAPS-based vaccine containing complexes of 24 serotype-specific polysaccharides (PS), non-covalently coupled with fusion protein 1 (CP1). This study evaluated the safety and immunogenicity of different dose levels of Pn-MAPS24v, administered in Japanese adults either subcutaneously (SC) or intramuscularly (IM).

Methods

In this phase 1, dose-escalation, observer-blind trial conducted in Japan, 54 pneumococcal vaccine-naïve adults aged 20–49 years (stage 1), and 72 adults aged 65–85 years (stage 2) were sequentially enrolled. In stage 1, participants were randomized 1:1 (SC:IM) to receive a single Pn-MAPS24v dose at one of the dose levels (1 μg, 2 μg, or 5 μg per PS). In stage 2, participants were randomized 3:1 (Pn-MAPS24v:23-valent pneumococcal polysaccharide vaccine [PPSV23]) and 1:1 (SC:IM) to receive a single dose of either Pn-MAPS24v (one of three dose levels), or PPSV23. Solicited adverse events (AEs) were collected through 7 days post-vaccination, and treatment-emergent AEs (TEAEs) up to 1 month post-vaccination. Serotype-specific opsonophagocytic activity titers and immunoglobulin G (IgG) concentrations, as well as anti-CP1 IgG concentrations were measured before and 1 month post-vaccination.

Results

No safety or reactogenicity concerns were identified in any age category across groups. No grade 3–4 TEAEs, serious AEs, or deaths were reported. Regardless of the age category, dose level, administration route, or study vaccine, the frequency of reported TEAEs was low and all vaccine-related TEAEs were mild. Pain, tenderness, and fatigue were the most frequently reported solicited AEs. One month post-vaccination, Pn-MAPS24v induced serotype-specific immune responses that were comparable or higher than those elicited by PPSV23. The immune responses were similar after SC and IM administration.

Conclusion

Pn-MAPS24v showed an acceptable safety profile and was immunogenic after SC and IM administration, therefore supporting the further development of Pn-MAPS24v in Japan.

ClinicalTrials.gov: NCT04265911