tetano
Editor, Senior Moderator
EBioMedicine
. 2022 Nov 11;86:104341.
doi: 10.1016/j.ebiom.2022.104341. Online ahead of print.
Multivalent S2-based vaccines provide broad protection against SARS-CoV-2 variants of concern and pangolin coronaviruses
Peter J Halfmann[SUP] 1 [/SUP], Steven J Frey[SUP] 2 [/SUP], Kathryn Loeffler[SUP] 2 [/SUP], Makoto Kuroda[SUP] 1 [/SUP], Tadashi Maemura[SUP] 1 [/SUP], Tammy Armbrust[SUP] 1 [/SUP], Jie E Yang[SUP] 3 [/SUP], Yixuan J Hou[SUP] 4 [/SUP], Ralph Baric[SUP] 5 [/SUP], Elizabeth R Wright[SUP] 3 [/SUP], Yoshihiro Kawaoka[SUP] 6 [/SUP], Ravi S Kane[SUP] 7 [/SUP]
Affiliations
Abstract
Background: The COVID-19 pandemic continues to cause morbidity and mortality worldwide. Most approved COVID-19 vaccines generate a neutralizing antibody response that primarily targets the highly variable receptor-binding domain (RBD) of the SARS-CoV-2 spike (S) protein. SARS-CoV-2 "variants of concern" have acquired mutations in this domain allowing them to evade vaccine-induced humoral immunity. Recent approaches to improve the breadth of protection beyond SARS-CoV-2 have required the use of mixtures of RBD antigens from different sarbecoviruses. It may therefore be beneficial to develop a vaccine in which the protective immune response targets a more conserved region of the S protein.
Methods: Here we have developed a vaccine based on the conserved S2 subunit of the S protein and optimized the adjuvant and immunization regimen in Syrian hamsters and BALB/c mice. We have characterized the efficacy of the vaccine against SARS-CoV-2 variants and other coronaviruses.
Findings: Immunization with S2-based constructs elicited a broadly cross-reactive IgG antibody response that recognized the spike proteins of not only SARS-CoV-2 variants, but also SARS-CoV-1, and the four endemic human coronaviruses. Importantly, immunization reduced virus titers in respiratory tissues in vaccinated animals challenged with SARS-CoV-2 variants B.1.351 (beta), B.1.617.2 (delta), and BA.1 (omicron) as well as a pangolin coronavirus.
Interpretation: These results suggest that S2-based constructs can elicit a broadly cross-reactive antibody response resulting in limited virus replication, thus providing a framework for designing vaccines that elicit broad protection against coronaviruses.
Funding: NIH, Japan Agency for Medical Research and Development, Garry Betty/ V Foundation Chair Fund, and NSF.
Keywords: COVID-19; Coronavirus; SARS-CoV-2; Vaccine.
. 2022 Nov 11;86:104341.
doi: 10.1016/j.ebiom.2022.104341. Online ahead of print.
Multivalent S2-based vaccines provide broad protection against SARS-CoV-2 variants of concern and pangolin coronaviruses
Peter J Halfmann[SUP] 1 [/SUP], Steven J Frey[SUP] 2 [/SUP], Kathryn Loeffler[SUP] 2 [/SUP], Makoto Kuroda[SUP] 1 [/SUP], Tadashi Maemura[SUP] 1 [/SUP], Tammy Armbrust[SUP] 1 [/SUP], Jie E Yang[SUP] 3 [/SUP], Yixuan J Hou[SUP] 4 [/SUP], Ralph Baric[SUP] 5 [/SUP], Elizabeth R Wright[SUP] 3 [/SUP], Yoshihiro Kawaoka[SUP] 6 [/SUP], Ravi S Kane[SUP] 7 [/SUP]
Affiliations
- PMID: 36375316
- DOI: 10.1016/j.ebiom.2022.104341
Abstract
Background: The COVID-19 pandemic continues to cause morbidity and mortality worldwide. Most approved COVID-19 vaccines generate a neutralizing antibody response that primarily targets the highly variable receptor-binding domain (RBD) of the SARS-CoV-2 spike (S) protein. SARS-CoV-2 "variants of concern" have acquired mutations in this domain allowing them to evade vaccine-induced humoral immunity. Recent approaches to improve the breadth of protection beyond SARS-CoV-2 have required the use of mixtures of RBD antigens from different sarbecoviruses. It may therefore be beneficial to develop a vaccine in which the protective immune response targets a more conserved region of the S protein.
Methods: Here we have developed a vaccine based on the conserved S2 subunit of the S protein and optimized the adjuvant and immunization regimen in Syrian hamsters and BALB/c mice. We have characterized the efficacy of the vaccine against SARS-CoV-2 variants and other coronaviruses.
Findings: Immunization with S2-based constructs elicited a broadly cross-reactive IgG antibody response that recognized the spike proteins of not only SARS-CoV-2 variants, but also SARS-CoV-1, and the four endemic human coronaviruses. Importantly, immunization reduced virus titers in respiratory tissues in vaccinated animals challenged with SARS-CoV-2 variants B.1.351 (beta), B.1.617.2 (delta), and BA.1 (omicron) as well as a pangolin coronavirus.
Interpretation: These results suggest that S2-based constructs can elicit a broadly cross-reactive antibody response resulting in limited virus replication, thus providing a framework for designing vaccines that elicit broad protection against coronaviruses.
Funding: NIH, Japan Agency for Medical Research and Development, Garry Betty/ V Foundation Chair Fund, and NSF.
Keywords: COVID-19; Coronavirus; SARS-CoV-2; Vaccine.