Safety, tolerability and immunogenicity of a novel 24-valent pneumococcal vaccine in toddlers: A phase 1 randomized controlled trial

Background: Pneumococcal conjugate vaccines (PCVs) significantly reduced pneumococcal disease burden. Nevertheless, alternative approaches for controlling more serotypes are needed. Here, the safety, tolerability, and immunogenicity of a 24-valent (1/2/3/4/5/6A/6B/7F/8/9N/9V/10A/11A/12F/14/15B/17F/18C/19A/19F/ 20B/22F/23F/33F) pneumococcal vaccine based on Multiple Antigen-Presenting System (MAPS) technology (Pn-MAPS24v) was assessed in toddlers. Methods: In this phase 1, blinded, dose-escalation, active-controlled multicenter study conducted in the United States (September/2020-April/2022), 12-15-month-old toddlers primed with three doses of 13-valent PCV (PCV13) were randomized 3:2 to receive a single dose of one of three Pn-MAPS24v dose levels (1 mu g/2 mu g/5 mu g per polysaccharide) or PCV13 intramuscularly. Reactogenicity (within 7 days), treatment-emergent adverse events (TEAEs, within 180 days), serious/medically attended adverse events (SAEs/MAAEs, within 180 days), and immunogenicity (serotype-specific anti-capsular polysaccharide immunoglobulin G [IgG] and opsonophagocytic activity [OPA] responses at 30 days post-vaccination) were assessed. Results: Of 75 toddlers enrolled, 74 completed the study (Pn-MAPS24v 1 mu g/2 mu g/5 mu g: 15/14/16, PCV13: 29). Frequencies of local (60 %/67 %/31 %) and systemic events (67 %/67 %/75 %) in the Pn-MAPS24v 1 mu g/2 mu g/5 mu g and the PCV13 (55 %, 79 %) groups were in similar ranges. TEAEs were reported by 47 %/40 %/63 % of PnMAPS24v 1 mu g/2 mu g/5 mu g recipients and 52 % of PCV13 recipients. No vaccine-related SAE was reported. At 30 days post-vaccination, for each of the 13 common serotypes, >= 93 % of participants in each group had IgG concentrations >= 0.35 mu g/mL; >92 % had OPA titers >= lower limit of quantitation (LLOQ), except for serotype 1 (79 %). For 7/11 unique serotypes (2/8/9N/11A/17F/22F/33F), at all dose levels, >= 78 % of Pn-MAPS24v recipients in each group had IgG concentrations >= 0.35 mu g/mL and 80 %-100 % had OPA titers >= LLOQ. Conclusions: In 12-15-month-old toddlers, a single dose of Pn-MAPS24v showed an acceptable safety profile, regardless of dose level; AEs were reported at similar frequencies by Pn-MAPS24v and PCV13 recipients. PnMAPS24v elicited IgG and OPA responses to all common and most unique serotypes. These results support further clinical evaluation in infants.