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.