COVID-19 and Influenza Booster Vaccination Elicits Robust Antibody Responses in Patients with Primary Brain Tumors Comparable to Healthy Adults

<b>Background</b>: Patients with primary brain tumors face profound disease- and treatment-related immunosuppression, placing them at high risk for severe infections. Their capacity to mount protective immune responses to vaccination, particularly to repeated antigen exposures such as COVID-19 boosters, remains critically under-defined, leading to uncertainty in clinical practice. <b>Methods</b>: In this prospective cohort study, we analyzed humoral responses to seasonal COVID-19 (mRNA-based) and influenza vaccination in 17 patients with primary brain tumors (recruited from an initial cohort of 37) who received a booster shot, and 19 healthy controls. Serum samples were collected before (T1) and 30 ± 2 days after (T2) vaccination to quantify SARS-CoV-2 anti-Spike (S) IgG and anti-Influenza IgG titers. <b>Results</b>: Despite ongoing chemotherapy in 47% of patients, baseline anti-S antibody titers were comparable between groups. Following the booster, median anti-S titers increased significantly and to a similar magnitude in both patients (from 5030 to 18,500 BAU/mL; IQR: 13,885-24,420) and controls (from 4429 to 20,200 BAU/mL; IQR: 11,075-26,680; <i>p</i> = 0.6137, Mann-Whitney U test). Only two heavily pre-treated patients showed no booster response. All participants showed sero-positivity to Anti-Influenza IgG at baseline. For the primary brain tumor cohort, a significant increase for anti-Influenza IgG at T2 was observed (<i>p</i> = 0.0002). Mean antibody titers did not differ between both cohorts. <b>Conclusions</b>: Our findings provide evidence that patients with primary brain tumors can mount robust recall immunity to mRNA vaccines, addressing clinical uncertainty about booster efficacy in this population. These data provide a strong rationale for prioritizing booster vaccinations in this vulnerable population and argue for the inclusion of these patients in future pivotal vaccine trials.