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.

Keywords: 24-valent pneumococcal MAPS-based vaccine; Dose escalation; Immunogenicity; Japanese adults; Safety; Subcutaneous-intramuscular.