Boosting of Waned Humoral and Cellular Responses to SARS-CoV-2 Variants of Concern Among Patients with Cancer

This study offers longitudinal insight into the impact of three SARS-CoV-2 vaccinations on humoral and cellular immunity in patients with solid cancers, patients with hematologic malignancies, and persons without cancer. For all cohorts, virus-neutralizing immunity was significantly depleted over a period of up to 9 months following the second vaccine dose, the one striking exception being IL2 production by SARS-CoV-2 antigen-specific T cells. Immunity was restored by the third vaccine dose, except in a substantial number of patients with hematologic malignancy, for whom both cancer type and treatment schedule were associated with nonresponse. Thus, whereas most patients with myelodysplastic syndrome were conspicuously good responders, some patients with other hematologic malignancies receiving cancer therapies within 2 weeks of vaccination showed no seroconversion despite three vaccine doses. Moreover, SARS-CoV-2 exposure during the course of the study neither prevented immunity waning,even in healthy controls, nor guaranteed vaccine responsiveness. These data offer real-world human immunologic insights that can inform health policy for patients with cancer. Significance: Global health policy reliant on SARS-CoV-2 vaccine ef-fectiveness is underpinned by our understanding of the durability of protection offered by sequential vaccinations and the efficacy of boost-ing, especially in immunocompromised patient populations who might constitute virus reservoirs. Here, we have: (i) clarified in patients with can-cer the degree of waning of antibodies, serum neutralization titres against parental virus and variants of concern, and T-cell responses; (ii) evalu-ated the immune response among patients with cancer to a third dose of COVID-19 vaccine; and (iii) provided safety data following the third dose of the BNT162b2 COVID-19 vaccine in patients with cancer.