evidence: Owing to these advantages, two COVID-19 mRNA vaccines (Moderna mRNA-1273 and Pfizer/BioNTech BNT162b2) were authorized by the US Food and Drug Administration (FDA) for emergency use in under a year. Therefore, these early licensed mRNA vaccines were given priority in many countries. Around the same time or later, various COVID-19 vaccines, including inactivated and viral vector vaccines, were approved, and globally administered. Furthermore, the FDA has recently approved a traditional protein subunit type vaccine, Novavax, for emergency use8. Because of the availability of these vaccines, people worldwide have inadvertently received a heterologous prime-boost vaccination schedule, i.e., the administration of different types of vaccines to achieve immunization against a single virus. It has been reported that heterologous prime-boost strategies induce more robust T-cell responses and higher neutralizing antibody titers9. Increasing clinical results indicate that heterologous vaccination strategies such as priming with viral vectored vaccines followed by boosting with mRNA vaccines or priming with inactivated vaccines followed by boosting with mRNA vaccines against COVID-19 provided enhanced immune responses compared to homologous vaccination strategies10. However, the immunogenicity and efficacy of heterologous priming-boosting using mRNA and protein vaccines have not yet been reported.