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

Abstract

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.

Keywords: Anti-Spike antibodies; Antibody avidity; Immune Checkpoint inhibitors; MRNA vaccine; Neutralizing antibodies; SARS-CoV-2.

Fig. 1

Distribution of anti-RBD immunoglobulins. Distribution of IgG (a), IgM (b) and IgA (c) anti-RBD in solid cancer patients as compared with untreated hematological patients and health care workers (HCW), before the first dose (T0) and after the second (T2). Levels of IgG anti-RBD antibodies in 18 patients that received a third dose before the first dose (T0), after the second (T2) and after the third (T3) (d). Results are represented as odds ratio of a positive internal control (OR). p < 0.05 was considered as significant

Fig. 2

Neutralizing ability and avidity of anti-RBD antibodies. a The distribution of immunoglobulin inhibitory activity measured by SPIA kit before the first dose of vaccine (T0) and after the second (T2) in solid cancer patients, hematological subjects and health care workers (HCW). Levels of neutralizing antibodies in 18 solid cancer patients that received a third dose before the first dose (T0), after the second (T2) and after the third dose (T3) (b). Results are expressed as the percentage of inhibition of the binding of labeled ACE2 receptor to RBD coated plates. p < 0.05 was considered as significant. c The avidity of anti RBD IgG from vaccinated solid cancer patients after the second (T2) and after the third dose (T3). For the different urea concentrations, mean binding values and standard deviations obtained in each patient group are represented