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

© 2024. The Author(s)..

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.

Medienart:

E-Artikel

Erscheinungsjahr:

2024

Erschienen:

2024

Enthalten in:

Zur Gesamtaufnahme - volume:21

Enthalten in:

Virology journal - 21(2024), 1 vom: 09. Apr., Seite 82

Sprache:

Englisch

Beteiligte Personen:

Stepanova, Ekaterina [VerfasserIn]
Isakova-Sivak, Irina [VerfasserIn]
Mezhenskaya, Daria [VerfasserIn]
Niskanen, Sergei [VerfasserIn]
Matyushenko, Victoria [VerfasserIn]
Bazhenova, Ekaterina [VerfasserIn]
Rak, Alexandra [VerfasserIn]
Wong, Pei Fong [VerfasserIn]
Prokopenko, Polina [VerfasserIn]
Kotomina, Tatiana [VerfasserIn]
Krutikova, Elena [VerfasserIn]
Legotskiy, Sergei [VerfasserIn]
Neterebskii, Bogdan [VerfasserIn]
Ostroukhova, Tatiana [VerfasserIn]
Sivak, Konstantin [VerfasserIn]
Orshanskaya, Yana [VerfasserIn]
Yakovlev, Kirill [VerfasserIn]
Rudenko, Larisa [VerfasserIn]

Links:

Volltext

Themen:

Antibodies, Viral
Bivalent vaccine
COVID-19
COVID-19 Vaccines
Hemagglutinins
Immunogenicity
Influenza
Influenza Vaccines
Journal Article
Recombinant influenza virus
SARS-CoV-2
Spike Glycoprotein, Coronavirus
Spike protein, SARS-CoV-2
Syrian hamsters
Vaccines, Combined
Virus vectored vaccine

Anmerkungen:

Date Completed 10.04.2024

Date Revised 11.04.2024

published: Electronic

Citation Status MEDLINE

doi:

10.1186/s12985-024-02350-w

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM370792017