Repeated SARS-CoV-2 vaccination in cancer patients treated with immune checkpoint inhibitors: induction of high-avidity anti-RBD neutralizing antibodies.

BACKGROUND: Cancer patients are more vulnerable to COVID-19 and are thus given high priority in vaccination campaigns. In solid cancer patients treated with checkpoint inhibitors, we evaluated the amount of anti-RBD and neutralizing antibodies and antibody avidity after two or three doses of the vaccine. METHODS: Thirty-eight solid cancer patients, 15 untreated hematological patients and 21 healthy subjects were enrolled in the study. Blood was collected before the first dose (T0), 21 days after the second (T2) and in 18 solid cancer patients also 15 days after the third dose of vaccine (T3). IgG, IgM and IgA anti-RBD antibodies were detected by ELISA. Neutralizing antibodies were measured testing the inhibition of RBD binding to ACE2. Antibody avidity was evaluated in 18 patients by a urea avidity ELISA. RESULTS: IgG anti-RBD antibodies were produced in 65.8% of the cancer patients at T2, and in 60% of hematological patients at levels lower than healthy controls. IgM and IgA anti-RBD antibodies were also produced in 5.3% and 21% cancer patients, respectively. At T3, a significant increase in anti-RBD IgG levels was observed. Neutralizing antibodies were produced in 68.4% of cancer patients as compared with 93% of untreated hematological patients and 100% of controls, at titers lower than in healthy subjects. At T3, neutralizing antibodies and avidity of IgG anti-RBD increased; 6/18 patients negative at T2 developed neutralizing antibodies at T3. CONCLUSION: The data indicate that in cancer patients mRNA vaccine induces high avidity anti-RBD antibodies and neutralizing antibodies that increase after the third dose. The process of induction and selection of high-affinity antibodies is apparently unaffected by the treatment with anti-PD-1 or anti-PD-L1 antibodies.

Induction of neutralizing antibodies in CLL patients after SARS-CoV-2 mRNA vaccination: a monocentric experience.

Vaccination represents the best strategy to fight COVID-19 pandemics, especially in immune compromised subjects. In chronic lymphatic leukemia patients, a marked impairment of the immune response to mRNA SARS-CoV-2 vaccine was observed. In this report, we analyzed anti-RBD and neutralizing antibodies in CLL patients after two doses of mRNA SARS CoV 2 vaccine and evaluated the impact of Bruton kinase inhibitory agents. Twenty-seven CLL patients vaccinated with mRNA vaccines against SARS CoV-2 were recruited. Serum IgG, IgM and IgA anti-RBD antibodies and neutralizing antibodies were detected, and antibody avidity was measured. Peripheral blood leukocytes subsets were evaluated by flow cytometry. After two vaccine doses anti-RBD IgG were produced in 11/27 (40.5%) of patients and levels of IgG and IgA anti RBD in CLL patients were sensibly lower than in controls. Neutralizing antibodies were detectable in 12/27 (44.5%) of the patients and their level was lower than that observed in controls. Disease burden and treatment with Bruton kinases inhibitors markedly impaired vaccine induced antibody response. However, in responder patients, antibody avidity was comparable to normal subjects, indicating that the process of clonal selection and affinity maturation takes place as expected. Taken together, these data confirm the impact of disease burden and therapy on production of anti-RBD and neutralizing antibodies and support the current policy of vaccinating CLL patients.