tetano
Editor, Senior Moderator
Vaccines (Basel)
. 2022 Jul 18;10(7):1142.
doi: 10.3390/vaccines10071142.
Development of a T Cell-Based COVID-19 Vaccine Using a Live Attenuated Influenza Vaccine Viral Vector
Irina Isakova-Sivak[SUP] 1 [/SUP], Ekaterina Stepanova[SUP] 1 [/SUP], Victoria Matyushenko[SUP] 1 [/SUP], Sergei Niskanen[SUP] 2 [/SUP], Daria Mezhenskaya[SUP] 1 [/SUP], Ekaterina Bazhenova[SUP] 1 [/SUP], Elena Krutikova[SUP] 1 [/SUP], Tatiana Kotomina[SUP] 1 [/SUP], Polina Prokopenko[SUP] 1 [/SUP], Bogdan Neterebskii[SUP] 2 [/SUP], Aleksandr Doronin[SUP] 2 [/SUP], Elena Vinogradova[SUP] 2 [/SUP], Kirill Yakovlev[SUP] 3 [/SUP], Konstantin Sivak[SUP] 3 [/SUP], Larisa Rudenko[SUP] 1 [/SUP]
Affiliations
Abstract
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 NP[SUB]366[/SUB] 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.
Keywords: COVID-19 vaccine; HLA-A2.1 transgenic mice; SARS-CoV-2; Syrian hamsters; T-cell epitopes; cross-protection; influenza virus vector; live attenuated influenza vaccine.
. 2022 Jul 18;10(7):1142.
doi: 10.3390/vaccines10071142.
Development of a T Cell-Based COVID-19 Vaccine Using a Live Attenuated Influenza Vaccine Viral Vector
Irina Isakova-Sivak[SUP] 1 [/SUP], Ekaterina Stepanova[SUP] 1 [/SUP], Victoria Matyushenko[SUP] 1 [/SUP], Sergei Niskanen[SUP] 2 [/SUP], Daria Mezhenskaya[SUP] 1 [/SUP], Ekaterina Bazhenova[SUP] 1 [/SUP], Elena Krutikova[SUP] 1 [/SUP], Tatiana Kotomina[SUP] 1 [/SUP], Polina Prokopenko[SUP] 1 [/SUP], Bogdan Neterebskii[SUP] 2 [/SUP], Aleksandr Doronin[SUP] 2 [/SUP], Elena Vinogradova[SUP] 2 [/SUP], Kirill Yakovlev[SUP] 3 [/SUP], Konstantin Sivak[SUP] 3 [/SUP], Larisa Rudenko[SUP] 1 [/SUP]
Affiliations
- PMID: 35891306
- PMCID: PMC9318028
- DOI: 10.3390/vaccines10071142
Abstract
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 NP[SUB]366[/SUB] 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.
Keywords: COVID-19 vaccine; HLA-A2.1 transgenic mice; SARS-CoV-2; Syrian hamsters; T-cell epitopes; cross-protection; influenza virus vector; live attenuated influenza vaccine.