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Expression of the SARS-CoV-2 receptor-binding domain by live attenuated influenza vaccine virus as a strategy for designing a bivalent vaccine against COVID-19 and influenza
Virology Journal ( IF 4.8 ) Pub Date : 2024-04-09 , DOI: 10.1186/s12985-024-02350-w
Ekaterina Stepanova , Irina Isakova-Sivak , Daria Mezhenskaya , Sergei Niskanen , Victoria Matyushenko , Ekaterina Bazhenova , Alexandra Rak , Pei Fong Wong , Polina Prokopenko , Tatiana Kotomina , Elena Krutikova , Sergei Legotskiy , Bogdan Neterebskii , Tatiana Ostroukhova , Konstantin Sivak , Yana Orshanskaya , Kirill Yakovlev , Larisa Rudenko

Influenza and SARS-CoV-2 are two major respiratory pathogens that cocirculate in humans and cause serious illness with the potential to exacerbate disease in the event of co-infection. To develop a bivalent vaccine, capable of protecting against both infections, we inserted the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein into hemagglutinin (HA) molecule or into the open reading frame of the truncated nonstructural protein 1 (NS1) of live attenuated influenza vaccine (LAIV) virus and assessed phenotypic characteristics of the rescued LAIV-RBD viruses, as well as their immunogenicity in mouse and Syrian hamster animal models. A panel of 9 recombinant LAIV-RBD viruses was rescued using the A/Leningrad/17 backbone. Notably, only two variants with RBD insertions into the HA molecule could express sufficient quantities of RBD protein in infected MDCK cells. Intranasal immunization of mice induced high levels of anti-influenza antibody responses in all chimeric LAIV-RBD viruses, which was comparable to the LAIV virus vector. The RBD-specific antibody responses were most pronounced in the variant expressing RBD194 fragment as a chimeric HA protein. This candidate was further tested in Syrian hamsters and was shown to be immunogenic and capable of protecting animals against both infections.
更新日期:2024-04-09
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