Evaluating a multi-vaccine respiratory immunization strategy involving SARS-CoV-2, pneumococcal, and influenza vaccines in adults: A randomized, open-label, multicenter, controlled, non-inferiority Phase IV trial in China.

Co-administration of vaccines targeting multiple respiratory pathogens may enhance coverage and streamline adult immunization programs. We conducted a randomized, multicentre, open-label Phase IV trial registered at Chinese Clinical Trial Registry (ChiCTR2100046227) in China to evaluate the immunogenicity and safety of co-administering an inactivated SARS-CoV-2 vaccine (WIBP-CorV) with the 23-valent pneumococcal polysaccharide vaccine (PPV23) and a quadrivalent inactivated influenza vaccine (IIV4). A total of 1,404 adults aged ≥ 18 year, including equal numbers of adults aged 18-59 year and ≥60 year, were randomized 1:1:1 to receive WIBP-CorV + PPV23 on Day 0 followed by WIBP-CorV + IIV4 on Day 28, WIBP-CorV alone on Days 0 and 28, or PPV23 on Day 0 followed by IIV4 on Day 28. Co-administration preserved humoral immune responses across vaccine platforms. Non-inferiority in geometric mean titers or concentrations was demonstrated for SARS-CoV-2 neutralizing antibodies and pneumococcal serotype-specific IgG responses. Seroconversion rates were non-inferior to those following separate administration for all pneumococcal serotypes, though results were less consistent for SARS-CoV-2 (after the second dose) and influenza A(H1N1). Age-stratified analyses showed age- and strain-specific non-inferiority findings that should be interpreted cautiously. Co-administration demonstrated an acceptable safety profile, with only slightly higher rates of mild, transient local reactions and no vaccine-related serious adverse events (SAEs). These findings support the feasibility of co-administering WIBP-CorV with PPV23 and IIV4 while maintaining immunogenicity and safety in adults represented in this study.Trial registration The study was registered in the Chinese Clinical Trial Registry (ChiCTR) under registration number ChiCTR2100046227.