tetano
Editor, Senior Moderator
Virol J
. 2024 Apr 9;21(1):82.
doi: 10.1186/s12985-024-02350-w. 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
Ekaterina Stepanova[SUP] 1 [/SUP], Irina Isakova-Sivak[SUP] 2 [/SUP], Daria Mezhenskaya[SUP] 2 [/SUP], Sergei Niskanen[SUP] 3 [/SUP], Victoria Matyushenko[SUP] 2 [/SUP], Ekaterina Bazhenova[SUP] 2 [/SUP], Alexandra Rak[SUP] 2 [/SUP], Pei Fong Wong[SUP] 2 [/SUP], Polina Prokopenko[SUP] 2 [/SUP], Tatiana Kotomina[SUP] 2 [/SUP], Elena Krutikova[SUP] 2 [/SUP], Sergei Legotskiy[SUP] 3 [/SUP], Bogdan Neterebskii[SUP] 3 [/SUP], Tatiana Ostroukhova[SUP] 3 [/SUP], Konstantin Sivak[SUP] 4 [/SUP], Yana Orshanskaya[SUP] 4 [/SUP], Kirill Yakovlev[SUP] 4 [/SUP], Larisa Rudenko[SUP] 2 [/SUP]
Affiliations
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.
Keywords: Bivalent vaccine; COVID-19; Immunogenicity; Influenza; Recombinant influenza virus; SARS-CoV-2; Syrian hamsters; Virus vectored vaccine.
. 2024 Apr 9;21(1):82.
doi: 10.1186/s12985-024-02350-w. 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
Ekaterina Stepanova[SUP] 1 [/SUP], Irina Isakova-Sivak[SUP] 2 [/SUP], Daria Mezhenskaya[SUP] 2 [/SUP], Sergei Niskanen[SUP] 3 [/SUP], Victoria Matyushenko[SUP] 2 [/SUP], Ekaterina Bazhenova[SUP] 2 [/SUP], Alexandra Rak[SUP] 2 [/SUP], Pei Fong Wong[SUP] 2 [/SUP], Polina Prokopenko[SUP] 2 [/SUP], Tatiana Kotomina[SUP] 2 [/SUP], Elena Krutikova[SUP] 2 [/SUP], Sergei Legotskiy[SUP] 3 [/SUP], Bogdan Neterebskii[SUP] 3 [/SUP], Tatiana Ostroukhova[SUP] 3 [/SUP], Konstantin Sivak[SUP] 4 [/SUP], Yana Orshanskaya[SUP] 4 [/SUP], Kirill Yakovlev[SUP] 4 [/SUP], Larisa Rudenko[SUP] 2 [/SUP]
Affiliations
- PMID: 38589848
- PMCID: PMC11003101
- DOI: 10.1186/s12985-024-02350-w
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.
Keywords: Bivalent vaccine; COVID-19; Immunogenicity; Influenza; Recombinant influenza virus; SARS-CoV-2; Syrian hamsters; Virus vectored vaccine.