A Single Vaccine Protects against SARS-CoV-2 and Influenza Virus in Mice

Abstract

The ongoing SARS-CoV-2 pandemic posed a severe global threat on public health, as do so by influenza viruses (influenza) and other coronaviruses. Here we present chimpanzee adenovirus 68 (AdC68)-based vaccines designed to universally target coronaviruses and influenza. Our design is centered on an immunogen generated by fusing the SARS-CoV-2 receptor-binding domain (RBD) to the conserved stalk of H7N9 hemagglutinin (HA). Remarkably, the constructed vaccine effectively induced both SARS-CoV-2-targeting antibodies and anti-influenza antibodies in mice, consequently affording protection from lethal SARS-CoV-2 and H7N9 challenges and effective H3N2 control. We propose our AdC68 vectored coronavirus-influenza vaccine as a universal approach toward curbing respiratory virus-causing pandemics. IMPORTANCE The COVID-19 pandemic exemplifies the severe public health threat of respiratory virus infection, as do so by influenza A viruses. The currently envisioned strategy for prevention of respiratory virus-causing diseases requires comprehensive administration of vaccines tailored for individual virus. Here we present an alternative strategy by designing chimpanzee adenovirus 68-based vaccines targeting both SARS-CoV-2 receptor-binding-domain and conserved stalk of influenza hemagglutinin. When tested in mice, this strategy attained potent neutralizing antibodies against wild-type SARS-CoV-2 as well as its emerging variants, enabling an effective protection against lethal SARS-CoV-2 challenge. Notably, it also entitled a complete protection from lethal H7N9 challenge and efficient control of H3N2-induced morbidity. Our study opens a new avenue to universally curb respiratory virus infection by vaccination.