Summary
During the Coronavirus Disease 2019 pandemic, triggered by the SARS-CoV-2 virus, global vaccination strategies are remarkably effective. However, as the pandemic progressed, viral escape from antibody responses to vaccines emerged (Variants Of Concern – VOC). Studies moreover showed that natural infection combined with vaccination provide superior immunity relative to vaccination alone. As natural infection has the possibility to provide a broader immune response from T-cells recognizing viral protein fragments (peptides) not currently included in standard vaccines, mapping of the T-cell response to infection would provide important insights into which parts of the virus have the capacity to evoke strong responses. In the thesis Isaac Blaas and co-workers found that out of 123 candidate targets in SARS-CoV-2, 29 evoked a response in CD8 T-cells in a large cohort of 83 otherwise healthy individuals. Out of these 29, a set of only nine targets could induce a response in 83% of the investigated population. Strikingly, only two of nine derived from the Spike protein utilized in commercial vaccines, indicating that broader vaccine responses could be elicited from vaccines including a wider range of viral proteins. Blaas and co-workers demonstrated that VOC are not driven by escape to T-cell immunity, and that T-cell responses are conserved among VOC. Moreover, they demonstrated that in lymphoma patients lacking antibody responses to SARS-CoV-2 vaccination due to B-cell depleting cancer treatment, T-cell responses to vaccination were comparable with those in healthy controls. This indicates that lymphoma patients benefit from standard SARS-CoV-2 mRNA vaccines, but also that these patients might have enhanced effects if vaccines incorporating a wider range of viral targets giving T-cell responses were administered. Taken together, the thesis provides new insights into natural and vaccine-induced immune responses to SARS-CoV-2 that can improve vaccine design.
More info about the public defence
Blaas will give a Trial lecture the same day at 10:15 on the given topic: "T cell based vaccines against cancer".