Safety and immunogenicity of a 25-valent pneumococcal conjugate vaccine in pneumococcal vaccine-naive healthy adults: Results from 2 randomised, controlled clinical trials

BACKGROUND: Pneumococcus causes substantial morbidity and mortality worldwide in children under 5. IVT PCV-25 is a 25-valent pneumococcal conjugate vaccine (PCV25) designed to prevent invasive pneumococcal disease from the serotypes predominant in children, particularly in low and middle income countries (LMICs). METHODS: We completed 2 randomised, parallel-group, double-blind clinical trials in Canada to evaluate the safety and immunogenicity of a single IM dose of PCV25 in healthy adults who had no history of pneumococcal vaccination or microbiologically confirmed IPD. PCV20 (Prevnar 20) was the control. In CVIA 096, 30 participants per group were randomised to PCV25 at a dose similar to PCV 20 (2.2 μg for each serotype polysaccharide (except 4.4 μg for serotype 6B) with 125 μg aluminium as aluminium phosphate (2.2/125)) or PCV20. Potentially more immunogenic formulations with higher polysaccharide and/or aluminium phosphate dose were evaluated in CVIA105, where 40 participants were randomised to PCV25 (2.2/125), 60 to PCV25 (2.2/250), 80 to PCV25 (4.4/250), and 40 to PCV20. RESULTS: Most participants were female and white. All participants were included in the safety analyses. One participant in CVIA 096 and 6 participants in CVIA 105 were excluded from the immunogenicity analyses because of protocol deviations that might interfere with immune response. Solicited and unsolicited AE profiles were similar for PCV25 and PCV20. No Grade 4 events were reported. At the highest dose, PCV25 elicited IgG and OPA responses with GMFRs of ≥2 for all 25 serotypes and for serotype 6A except for OPA response to 35B. CONCLUSIONS: Multiple formulations of IVT PCV-25, a vaccine designed to cover pneumococcal serotypes prevalent in LMICs, were well tolerated and immunogenic in healthy adults. As adult immunogenicity is not fully predictive for infants, further development will evaluate safety and immunogenicity in the target infant population. CLINICALTRIALS: govNCT05540028,NCT06077656.