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

被引：14

作者：

Isakova-Sivak, Irina ^{[1
]}

Stepanova, Ekaterina ^{[1
]}

Matyushenko, Victoria ^{[1
]}

Niskanen, Sergei ^{[2
]}

Mezhenskaya, Daria ^{[1
]}

Bazhenova, Ekaterina ^{[1
]}

Krutikova, Elena ^{[1
]}

Kotomina, Tatiana ^{[1
]}

Prokopenko, Polina ^{[1
]}

Neterebskii, Bogdan ^{[2
]}

Doronin, Aleksandr ^{[2
]}

Vinogradova, Elena ^{[2
]}

Yakovlev, Kirill ^{[3
]}

Sivak, Konstantin ^{[3
]}

Rudenko, Larisa ^{[1
]}

机构：

[1] Inst Expt Med, St Petersburg 197022, Russia

[2] Joint Stock Co BIOCAD JSC BIOCAD St Petersburg, 38 Svyazi Str, St Petersburg 198515, Russia

[3] Smorodintsev Res Inst Influenza, St Petersburg 197376, Russia

来源：

VACCINES | 2022年 / 10卷 / 07期

关键词：

SARS-CoV-2; COVID-19; vaccine; influenza virus vector; live attenuated influenza vaccine; T-cell epitopes; HLA-A2; 1 transgenic mice; Syrian hamsters; cross-protection; SARS-COV-2; VARIANTS; RESPONSES; MICE; PEPTIDE;

D O I：

10.3390/vaccines10071142

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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.

引用

页数：27

共 78 条

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