Immunogenicity of Pfizer mRNA COVID-19 vaccination followed by J&J adenovirus COVID-19 vaccination in two CLL patients.

Importance: Individuals with Chronic Lymphocytic Leukemia have significant immune disfunction, often further disrupted by treatment. While currently available COVID-19 vaccinations are highly effective in immunocompetent individuals, they are often poorly immunogenic in CLL patients. It is important to understand the role heterologous boost would have in patients who did not respond to the recommended two-dose mRNA vaccine series with a SARS-CoV-2 specific immune response.

Objective: To characterize the immune response of two CLL patients who failed to seroconvert after initial mRNA vaccine series following a third, heterologous, COVID-19 vaccination with Ad26.COV2.S.

Design: Two subjects with CLL were enrolled in an IRB-approved observational longitudinal cohort study of the immune response to COVID-19 vaccination. After enrollment, they received a third vaccination with Ad26.COV2.S. Blood was drawn prior to original vaccination series, four weeks after mRNA vaccination, and again four weeks after third vaccination.

Setting: Eligible subjects were approached by oncologist overseeing CLL treatment and informed about study, at time of enrollment subjects consented to join the cohort study.

Participants: Sixteen subjects enrolled in the larger CLL cohort study, of whom two subjects received a third COVID-19 vaccination and were included in this analysis. Subject 1 is CLL treatment naive, while Subject 2 is currently on active treatment.

Main Outcomes And Measures: SARS-CoV-2 specific immune response, including plasma antibodies, memory B-cells, CD4 and CD8 T-cells were assessed prior to vaccination (baseline) as well as post vaccination series and post third dose.

Results: Of the two subjects who received Ad26.COV2.S doses, Subject 1 seroconverted, had RBD-specific memory B-cells as well as spike-specific CD4 T-cells while Subject 2 did not. Both subjects had a spike-specific CD8 T-cell response after original mRNA vaccination series that was further boosted after third dose (Subject 1), or remained stable (Subject 2).

Conclusions And Relevance: The results of this study, however small, is especially promising to CLL individuals who did not seroconvert following initial mRNA vaccination series. Especially those that are treatment naive, not currently in active treatment, or who may consider vaccination before beginning active treatment.