Immune Responses to COVID-19 mRNA Vaccines in Patients with Solid Tumors on Active, Immunosuppressive Cancer Therapy

Shroff, Rachna T.; Chalasani, Pavani; Wei, Ran; Pennington, Daniel; Quirk, Grace; Schoenle, Marta V.; Uhrlaub, Jennifer L.; Ripperger, Tyler J.; Jergović, Mladen; Dalgai, Shelby; Wolf, Alexander; Hammad, Hytham; Carrier, Amy; Scott, Aaron J.; Nikolich-Žugich, Janko; Worobey, Michael; Sprissler, Ryan; Dake, Michael; LaFleur, Bonnie J.; Bhattacharya, Deepta

Vaccines against SARS-CoV-2 have shown high efficacy, but immunocompromised participants were excluded from controlled clinical trials. We evaluated immune responses to the Pfizer/BioNTech mRNA vaccine in solid tumor patients (n=52) on active cytotoxic anti-cancer therapy. These responses were compared to a control cohort that also received the Pfizer/BioNTech vaccine (n=50). Using live SARS-CoV-2 assays, neutralizing antibodies were detected in 67% and 80% of cancer patients after the first and second immunizations, respectively, with a 3-fold increase in median titers after the booster. Similar trends were observed in serum antibodies against the receptor-binding domain (RBD) and S2 regions of Spike protein, and in IFNγ+Spike-specific T cells. The magnitude of each of these responses was diminished relative to the control cohort. We therefore quantified RBD− and Spike S1-specific memory B cell subsets as predictors of anamnestic responses to viral exposures or additional immunizations. After the second vaccination, Spike-specific plasma cell-biased memory B cells were observed in most cancer patients at levels similar to those of the control cohort after the first immunization. These data suggest that a third immunization might elevate antibody responses in cancer patients to levels seen in healthy individuals after the second dose. Trials should be conducted to test these predictions.