Multiantigen pan-sarbecovirus DNA vaccines generate protective T cell immune responses

Bergen, J. van; Camps, M.G.M.; Pardieck, I.N.; Veerkamp, D.; Leung, W.Y.; Leijs, A.A.; ... ; Ossendorp, F. (2023)

Article / Letter to editor

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 hospitalization and death caused by outbreaks of such viruses. We report the design and preclinical testing of 2 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 nonstructural proteins, and the other (CoVAX_MNS) encoded antigens from structural proteins. Both multiantigen 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 multiantigen 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 Ab 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 angiotensin-converting enzyme 2–transgenic mice. These results support clinical testing of these universal sarbecovirus vaccines for pandemic preparedness.

• All authors: Bergen, J. van; Camps, M.G.M.; Pardieck, I.N.; Veerkamp, D.; Leung, W.Y.; Leijs, A.A.; Myeni, S.K.; Kikkert, M.; Arens, R.; Zondag, G.C.; Ossendorp, F.
• Date: 2023-11-08
• Journal: JCI Insight
• Volume: 8
• Issue: 21
• DOI: doi:10.1172/jci.insight.172488
• Link: https://insight.jci.org/articles/view/172488