tetano
Editor, Senior Moderator
JCI Insight
. 2023 Sep 14;e172488.
doi: 10.1172/jci.insight.172488. Online ahead of print. Multi-antigen pan-sarbecovirus DNA vaccines generate protective T cell immune responses
Jeroen van Bergen[SUP] 1 [/SUP], Marcel Camps[SUP] 2 [/SUP], Iris N Pardieck[SUP] 2 [/SUP], Dominique Veerkamp[SUP] 2 [/SUP], Wing Yan Leung[SUP] 3 [/SUP], Anouk A Leijs[SUP] 4 [/SUP], Sebenzile K Myeni[SUP] 4 [/SUP], Marjolein Kikkert[SUP] 4 [/SUP], Ramon Arens[SUP] 2 [/SUP], Gerben C Zondag[SUP] 3 [/SUP], Ferry Ossendorp[SUP] 2 [/SUP]
Affiliations
SARS-CoV-2 is the third zoonotic coronavirus to cause a major outbreak in humans in recent years, and many more SARS-like coronaviruses with pandemic potential are circulating in several animal species. Vaccines inducing T cell immunity against broadly conserved viral antigens may protect against hospitalisation and death caused by outbreaks such viruses. We report the design and pre-clinical testing of two T-cell-based pan-sarbecovirus vaccines, based on conserved regions within viral proteins of sarbecovirus isolates of human and other carrier animals, like bats and pangolins. One vaccine (CoVAX_ORF1ab) encoded antigens derived from non-structural proteins, the other (CoVAX_MNS) antigens from structural proteins. Both multi-antigen DNA vaccines contained a large set of antigens shared across sarbecoviruses and were rich in predicted and experimentally validated human T cell epitopes. In mice, the multi-antigen vaccines generated both CD8 and CD4 T cell responses to shared epitopes. Upon encounter of full-length spike antigen, CoVAX_MNS-induced CD4 T cells were responsible for accelerated CD8 T cell and IgG antibody responses specific to the incoming spike, irrespective of its sarbecovirus origin. Finally, both vaccines elicited partial protection against a lethal SARS-CoV-2 challenge in human-ACE2-transgenic mice. These results support clinical testing of this universal sarbecovirus vaccine for pandemic preparedness.
Keywords: COVID-19; MHC class 1; MHC class 2; T cells; Vaccines.
. 2023 Sep 14;e172488.
doi: 10.1172/jci.insight.172488. Online ahead of print. Multi-antigen pan-sarbecovirus DNA vaccines generate protective T cell immune responses
Jeroen van Bergen[SUP] 1 [/SUP], Marcel Camps[SUP] 2 [/SUP], Iris N Pardieck[SUP] 2 [/SUP], Dominique Veerkamp[SUP] 2 [/SUP], Wing Yan Leung[SUP] 3 [/SUP], Anouk A Leijs[SUP] 4 [/SUP], Sebenzile K Myeni[SUP] 4 [/SUP], Marjolein Kikkert[SUP] 4 [/SUP], Ramon Arens[SUP] 2 [/SUP], Gerben C Zondag[SUP] 3 [/SUP], Ferry Ossendorp[SUP] 2 [/SUP]
Affiliations
- PMID: 37707962
- DOI: 10.1172/jci.insight.172488
SARS-CoV-2 is the third zoonotic coronavirus to cause a major outbreak in humans in recent years, and many more SARS-like coronaviruses with pandemic potential are circulating in several animal species. Vaccines inducing T cell immunity against broadly conserved viral antigens may protect against hospitalisation and death caused by outbreaks such viruses. We report the design and pre-clinical testing of two T-cell-based pan-sarbecovirus vaccines, based on conserved regions within viral proteins of sarbecovirus isolates of human and other carrier animals, like bats and pangolins. One vaccine (CoVAX_ORF1ab) encoded antigens derived from non-structural proteins, the other (CoVAX_MNS) antigens from structural proteins. Both multi-antigen DNA vaccines contained a large set of antigens shared across sarbecoviruses and were rich in predicted and experimentally validated human T cell epitopes. In mice, the multi-antigen vaccines generated both CD8 and CD4 T cell responses to shared epitopes. Upon encounter of full-length spike antigen, CoVAX_MNS-induced CD4 T cells were responsible for accelerated CD8 T cell and IgG antibody responses specific to the incoming spike, irrespective of its sarbecovirus origin. Finally, both vaccines elicited partial protection against a lethal SARS-CoV-2 challenge in human-ACE2-transgenic mice. These results support clinical testing of this universal sarbecovirus vaccine for pandemic preparedness.
Keywords: COVID-19; MHC class 1; MHC class 2; T cells; Vaccines.