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

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 doma...

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Published in:	Virology journal Vol. 21; no. 1; p. 82
Main Authors:	Stepanova, Ekaterina, Isakova-Sivak, Irina, Mezhenskaya, Daria, Niskanen, Sergei, Matyushenko, Victoria, Bazhenova, Ekaterina, Rak, Alexandra, Wong, Pei Fong, Prokopenko, Polina, Kotomina, Tatiana, Krutikova, Elena, Legotskiy, Sergei, Neterebskii, Bogdan, Ostroukhova, Tatiana, Sivak, Konstantin, Orshanskaya, Yana, Yakovlev, Kirill, Rudenko, Larisa
Format:	Journal Article
Language:	English
Published:	England BioMed Central Ltd 09-04-2024 BioMed Central BMC
Subjects:	Animal models Animals Antibiotics Antibodies, Viral Antigens Bivalent vaccine Cell culture Chemical properties Clinical trials COVID-19 COVID-19 Vaccines Genes Genetic engineering Genetic vectors HA protein Hamsters Hemagglutinins Humans Immunization Immunogenicity Influenza Influenza vaccines Influenza Vaccines - genetics Influenza viruses Influenza, Human Lectins Medical research Medicine, Experimental Mice Peptides Plasmids Proteins Recombinant influenza virus Respiratory diseases SARS-CoV-2 SARS-CoV-2 - genetics Severe acute respiratory syndrome coronavirus 2 Spike Glycoprotein, Coronavirus Spike protein Sucrose Testing Vaccines Vaccines, Combined Vectors (Biology) Virus vectored vaccine Viruses Wildlife conservation Russia Canada China Syria Germany United States > US Massachusetts COVID-19 Bivalent vaccine SARS-CoV-2 Immunogenicity Syrian hamsters Virus vectored vaccine Influenza Recombinant influenza virus
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Summary:	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.
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ISSN:	1743-422X 1743-422X
DOI:	10.1186/s12985-024-02350-w