Development of a T Cell-Based COVID-19 Vaccine Using a Live Attenuated Influenza Vaccine Viral Vector

• Published in: Vaccines (Basel) Vol. 10; no. 7; p. 1142
• Main Authors: Isakova-Sivak, Irina, Stepanova, Ekaterina, Matyushenko, Victoria, Niskanen, Sergei, Mezhenskaya, Daria, Bazhenova, Ekaterina, Krutikova, Elena, Kotomina, Tatiana, Prokopenko, Polina, Neterebskii, Bogdan, Doronin, Aleksandr, Vinogradova, Elena, Yakovlev, Kirill, Sivak, Konstantin, Rudenko, Larisa
• Format: Journal Article
• Language: English
• Published: Basel MDPI AG 18-07-2022; MDPI
• Subjects: Animals; Antibiotics; Antibodies; Antigens; Cell activation; Coronaviruses; COVID-19; COVID-19 vaccine; COVID-19 vaccines; Disease; Epitopes; Exo-a-sialidase; Genes; Hamsters; Histocompatibility antigen HLA; HLA-A2.1 transgenic mice; Immunization; Immunodominance; Immunological memory; Infections; Influenza; influenza virus vector; Leukocytes; Leukocytes (mononuclear); live attenuated influenza vaccine; Lymphocytes; Lymphocytes T; Memory cells; Pandemics; Peptides; Peripheral blood mononuclear cells; Plasmids; Proteins; Public health; Respiratory syncytial virus; SARS-CoV-2; Severe acute respiratory syndrome coronavirus 2; T-cell epitopes; Transgenic mice; Vaccines; Vectors (Biology); Viral diseases; Viruses; Weight loss; Weight reduction; United States > US; Germany; Russia
• ISSN: 2076-393X; 2076-393X
• DOI: 10.3390/vaccines10071142

The COVID-19 pandemic emerged in 2020 and has caused an unprecedented burden to all countries in the world. SARS-CoV-2 continues to circulate and antigenically evolve, enabling multiple reinfections. To address the issue of the virus antigenic variability, T cell-based vaccines are being developed, which are directed to more conserved viral epitopes. We used live attenuated influenza vaccine (LAIV) virus vector to generate recombinant influenza viruses expressing various T-cell epitopes of SARS-CoV-2 from either neuraminidase (NA) or non-structural (NS1) genes, via the P2A self-cleavage site. Intranasal immunization of human leukocyte antigen-A*0201 (HLA-A2.1) transgenic mice with these recombinant viruses did not result in significant SARS-CoV-2-specific T-cell responses, due to the immunodominance of NP366 influenza T-cell epitope. However, side-by-side stimulation of peripheral blood mononuclear cells (PBMCs) of COVID-19 convalescents with recombinant viruses and LAIV vector demonstrated activation of memory T cells in samples stimulated with LAIV/SARS-CoV-2, but not LAIV alone. Hamsters immunized with a selected LAIV/SARS-CoV-2 prototype were protected against challenge with influenza virus and a high dose of SARS-CoV-2 of Wuhan and Delta lineages, which was confirmed by reduced weight loss, milder clinical symptoms and less pronounced histopathological signs of SARS-CoV-2 infection in the lungs, compared to LAIV- and mock-immunized animals. Overall, LAIV is a promising platform for the development of a bivalent vaccine against influenza and SARS-CoV-2.