Objective To evaluate the safety of co-vaccination with domestic 23-valent pneumococcal polysaccharide vaccine (PPSV23) and split influenza virus vaccine (sFlu) in key populations aged 3 years and older and to provide a reference for formulating co-vaccination strategies.

Methods The study participants were 5 502 healthy and unhealthy (with chronic diseases) volunteers (including 2 072 children aged 3 – < 8 years, 1 598 residents aged 8 – < 60 years, and 1 832 elderly aged 60 years and older) vaccinated simultaneously with one dose of PPSV23 (intramuscular injection into the deltoid muscle of the left upper arm) and one dose of sFlu (into the right upper arm) in 8 cities of Anhui province from October 2021 to February 2023. Active surveillance for adverse reactions within 28 days of co-vaccination with PPSV23 and sFlu was conducted among participants through active reporting via the Ark Immunization mobile application and telephone or home interviews by health care workers. Reported current/historic chronic diseases and observed adverse events after co-vaccination were categorized according to the Medical Dictionary for Regulatory Activities (MedDRA) and the Guiding Principles for the Classification of Adverse Events in Clinical Trials of Preventive Vaccines issued by the National Medical Products Administration.

Results The prevalence of underlying chronic diseases was 1.45%, 100.00%, and 37.61% in participants aged 3 – < 8, 8 – < 60, and ≥ 60 years, respectively. All adverse events occurred within 7 days of co-vaccination, with an incidence rate of 2.67%. The incidence rates of grade 1, 2, and 3 adverse events were 1.62%, 0.93%, and 0.13%, respectively. The incidence rates of local and systemic adverse events were 2.25% and 1.00%, respectively. Local reactions were mainly pain at the vaccination site, while systemic reactions were mainly fever. The incidence of local adverse events was higher for PPSV23 than for sFlu when administered at the same time. The incidence rates of adverse reactions in participants aged 3 – < 8, 8 – < 60, and 60 years and older were 2.03%, 3.25%, and 2.89%, respectively, without significant difference (χ² = 5.741, P > 0.05). The grades of adverse reactions in the participants of the three age groups were mainly grade 1 and 2. The overall incidence rate of adverse reactions in healthy participants was 2.32% and that in unhealthy participants was 3.15%, without significant difference between the two groups (χ² = 3.530, P > 0.05). There were no significant differences in the incidence and severity of adverse events between the healthy and unhealthy participants aged 3 – < 8 years and 60 years and older (P > 0.05).

Conclusion Simultaneous vaccination with domestic PPSV23 and sFlu has shown good safety in key populations of different ages, health status and simultaneous vaccination with the two vaccines is recommended.