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.