ResearchIn-Press PreviewCOVID-19Vaccines
Open Access | 10.1172/jci.insight.172488
1Immunetune BV, Leiden, Netherlands
2Department of Immunology, Leiden University Medical Center (LUMC), Leiden, Netherlands
3Synvolux Therapeutics BV, Leiden, Netherlands
4Department of Medical Microbiology, Leiden University Medical Center (LUMC), Leiden, Netherlands
Find articles by van Bergen, J. in: JCI | PubMed | Google Scholar
1Immunetune BV, Leiden, Netherlands
2Department of Immunology, Leiden University Medical Center (LUMC), Leiden, Netherlands
3Synvolux Therapeutics BV, Leiden, Netherlands
4Department of Medical Microbiology, Leiden University Medical Center (LUMC), Leiden, Netherlands
Find articles by Camps, M. in: JCI | PubMed | Google Scholar
1Immunetune BV, Leiden, Netherlands
2Department of Immunology, Leiden University Medical Center (LUMC), Leiden, Netherlands
3Synvolux Therapeutics BV, Leiden, Netherlands
4Department of Medical Microbiology, Leiden University Medical Center (LUMC), Leiden, Netherlands
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1Immunetune BV, Leiden, Netherlands
2Department of Immunology, Leiden University Medical Center (LUMC), Leiden, Netherlands
3Synvolux Therapeutics BV, Leiden, Netherlands
4Department of Medical Microbiology, Leiden University Medical Center (LUMC), Leiden, Netherlands
Find articles by Veerkamp, D. in: JCI | PubMed | Google Scholar
1Immunetune BV, Leiden, Netherlands
2Department of Immunology, Leiden University Medical Center (LUMC), Leiden, Netherlands
3Synvolux Therapeutics BV, Leiden, Netherlands
4Department of Medical Microbiology, Leiden University Medical Center (LUMC), Leiden, Netherlands
Find articles by Leung, W. in: JCI | PubMed | Google Scholar
1Immunetune BV, Leiden, Netherlands
2Department of Immunology, Leiden University Medical Center (LUMC), Leiden, Netherlands
3Synvolux Therapeutics BV, Leiden, Netherlands
4Department of Medical Microbiology, Leiden University Medical Center (LUMC), Leiden, Netherlands
Find articles by Leijs, A. in: JCI | PubMed | Google Scholar
1Immunetune BV, Leiden, Netherlands
2Department of Immunology, Leiden University Medical Center (LUMC), Leiden, Netherlands
3Synvolux Therapeutics BV, Leiden, Netherlands
4Department of Medical Microbiology, Leiden University Medical Center (LUMC), Leiden, Netherlands
Find articles by Myeni, S. in: JCI | PubMed | Google Scholar
1Immunetune BV, Leiden, Netherlands
2Department of Immunology, Leiden University Medical Center (LUMC), Leiden, Netherlands
3Synvolux Therapeutics BV, Leiden, Netherlands
4Department of Medical Microbiology, Leiden University Medical Center (LUMC), Leiden, Netherlands
Find articles by Kikkert, M. in: JCI | PubMed | Google Scholar
1Immunetune BV, Leiden, Netherlands
2Department of Immunology, Leiden University Medical Center (LUMC), Leiden, Netherlands
3Synvolux Therapeutics BV, Leiden, Netherlands
4Department of Medical Microbiology, Leiden University Medical Center (LUMC), Leiden, Netherlands
Find articles by Arens, R. in: JCI | PubMed | Google Scholar
1Immunetune BV, Leiden, Netherlands
2Department of Immunology, Leiden University Medical Center (LUMC), Leiden, Netherlands
3Synvolux Therapeutics BV, Leiden, Netherlands
4Department of Medical Microbiology, Leiden University Medical Center (LUMC), Leiden, Netherlands
Find articles by Zondag, G. in: JCI | PubMed | Google Scholar
1Immunetune BV, Leiden, Netherlands
2Department of Immunology, Leiden University Medical Center (LUMC), Leiden, Netherlands
3Synvolux Therapeutics BV, Leiden, Netherlands
4Department of Medical Microbiology, Leiden University Medical Center (LUMC), Leiden, Netherlands
Find articles by Ossendorp, F. in: JCI | PubMed | Google Scholar
Published September 14, 2023 - More info
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.