1. Introduction
Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has had a huge negative impact on global public health and economic development.1 Since its discovery, SARS-CoV-2 has evolved into several variants, and now Omicron is a major public health concern owing to its high infectivity and antibody evasion.2 Omicron variants BA.4 and BA.5 were reported to be more transmissible and resistant to immunity than previous variants, including Omicron BA.1 and most monoclonal antibodies.2 As of November 2, 2023, SARS-CoV-2 and its variants had caused 771,679,618 confirmed cases and 6,977,023 deaths globally.3 Influenza A virus (IAV), a common respiratory infectious virus, causes severe respiratory illnesses in 3 to 5 million people and 290,000 to 650,000 deaths yearly worldwide.4 IAV is one of the most commonly recognized respiratory viruses identified as coinfected with SARS-CoV-2.5 Studies have shown that coinfection with SARS-CoV-2 during the acute stage of IAV infection further increases the risk of multiple tissue or organ disease in patients, leading to the occurrence of higher rates of severe illness and mortality.6-8 Vaccination is one of the most effective measures to prevent respiratory infectious viruses.
Seasonal vaccination against IAV could significantly decrease the number of individuals getting sick or death from the infection.9 Also, COVID-19 vaccination has effectively reduced severe cases and mortality rate.10, 11 Many dual-vaccination strategies are currently in the developmental stage, such as the virion-based vaccine,12, 13receptor-binding domain (RBD)-based vaccine,14RBD-conjugated inactivated IAV,15 mRNA vaccine,8 chimpanzee adenovirus 68 (AdC68)-based vaccine,16 and recombinant VSV-based bivalent vaccine.17 Similarly, we imagined the advantages of a combined SARS-CoV-2/IAV subunit vaccine in the fight against COVID-19 and influenza, including the safety and ease of producing such subunit vaccine on a large scale.
Accordingly, in this study, the immunogenicity and protective effect of an influenza/SARS-CoV-2 Omicron subunit combined vaccine adjuvanted with MF59 were evaluated in BALB/c mice. The combined vaccine induced high levels of IgG, IgG1, and IgG2aantibodies, as well as influenza A H1N1/California/2009 virus-specific hemagglutination-inhibiting antibodies in BALB/c mice. Furthermore, the subunit combined vaccine induced high titers of neutralizing antibodies against SARS-CoV-2 Omicron BA.5 pseudovirus and effectively reduced the viral load of SARS-CoV-2 Omicron BA.5.2 variant in the cell culture supernatants. Our study further demonstrated that the subunit combined vaccine achieved a double protective effect against influenza H1N1 A/California/07/2009 virus and SARS-CoV-2 Omicron BA.5.2 variant infection.