COVID-19 vaccinations in COVID-19 naïve population to predict utility of tumour-based vaccinations in glioma patients

Abstract Background Gliomas are the most common primary brain malignancy in adults, with treatment advances limited by challenges like the blood-brain barrier, tumour heterogeneity, and an immunosuppressive microenvironment. Tumour vaccines, such as adenoviral vector and mRNA-based vaccines, may overcome these barriers, but the ability of glioma patients to mount an immune response to these therapies remains unclear. This study assesses immune responses to adenoviral DNA and mRNA-based COVID-19 vaccinations in a glioma-enriched population as a model for glioma-based vaccine therapies. Methods COVID-19 naïve glioma and non-glioma solid tumour patients, along with healthy volunteers, were recruited between May 2021 and December 2022. Blood samples were collected at various time points: pre-vaccination, between the first and second doses, and at 1-, 3-, and 4-6-months post 2nd vaccination, including after a third booster dose. SARS-CoV-2 specific immune responses were evaluated using ELISA and ELISPOT assays. Results A total of 91 participants were analysed. At 1-month post 2nd vaccination, no significant differences in seroconversion rates were observed. By 3 months, glioma and non-glioma patients had significantly lower rates compared to healthy volunteers. Memory B and T cell responses were similar between glioma patients and healthy volunteers, but non-glioma patients showed decreased responses. Vaccine efficacy was comparable across all cohorts. Conclusion This study demonstrates that glioma patients can mount meaningful immune responses to DNA and mRNA vaccines, suggesting that glioma-based vaccine therapies are feasible and warrant further exploration.