Functional humoral and cellular response of monovalent COVID-19-vaccines against Omicron BA.2 variant of SARS-CoV-2 in patients with chronic lymphocytic leukemia

Abstract

We designed a prospective study to evaluate the humoral (using a surrogate virus neutralization test) and cellular (using an IFN-γ ELISpot) immune response among patients with chronic lymphocytic leukemia (CLL) against Wuhan-Hu-1 and Omicron BA.2 strains of SARS-CoV-2, after mRNA-based vaccination. The proportion of patients with a functional humoral response was higher among untreated CLL patients compared to treated CLL patients against both Wuhan-Hu-1 and Omicron BA.2 after the second and the third dose of vaccination, and at 12 months after the first dose. The proportion of positive cellular response against the peptide pool covering the full-length Wuhan-Hu-1 spike protein was similar between untreated and treated CLL patients at all three timepoints. The cellular response to the mutated regions of BA.2 spike protein was lower than the response to the corresponding regions in the ancestral spike after the second dose, but this difference was eliminated after the third dose.

Keywords:

• CLL
• vaccination
• cellular response
• Omicron

Acknowledgement

The authors thank the patients who participated in the study and their families and caregivers. A special thanks to Heather C. Darby for her patience and precision in storing and providing the samples when needed.

Author contributions

MP, TR, NEK, SAP, and RBK contributed to the study design. MP, TR, and JMM contributed to the study conduct, the laboratory assays, and the data analysis. MP, TR, NEK, ZT, TEW, SAP, and RBK. All the authors participated in the drafting and revising the manuscript, and approved the final version for submission.

Disclosure statement

No potential conflict of interest was reported by the author(s). NEK: Advisory Board for AbbVie, Astra Zeneca, Beigene, Behring, Boehringer Ingelheim Pharmaceuticals, Inc., Cytomx Therapy, Dava Oncology, Janssen, Juno Therapeutics, Oncotracker, Pharmacyclics and Targeted Oncology. DSMC (Data Safety Monitoring Committee) for: Agios Pharm, AstraZeneca, BMS –Celgene, Cytomx Therapeutics, Dren Bio Janssen, Morpho-sys, Rigel. RBK: Drs. Kennedy is an inventor on issued patents and pending patent applications related to vaccinia, measles, zika, and SARS-CoV-2 peptide vaccines. Drs. Kennedy has receive royalties from ICW Ventures for licensing intellectual property related to the development of peptide-based COVID-19 vaccines. Dr. Kennedy has received funding from Merck Research Laboratories to study waning immunity to mumps vaccine. These activities have been reviewed by the Mayo Clinic Conflict of Interest Review Board and are conducted in compliance with Mayo Clinic Conflict of Interest policies. This research has been reviewed by the Mayo Clinic Conflict of Interest Review Board and was conducted in compliance with Mayo Clinic Conflict of Interest policies. TEW: Clinical Trial Support to conduct clinical trials are provided by Celgene, Acerta, Incyte, Kura Oncology, Karyopharm. Advisory Board for ACD and Salarius Pharmaceutical.

Data availability statement

The dataset generated during the current study is available from the corresponding author on reasonable request.

Additional information

Funding

This study was funded by the Leukemia and Lymphoma Society and by the Mayo Clinic COVID-19 relief funds. SAP: Research funding has been provided to the institution from Janssen, AstraZeneca, Merck, and Genentech for clinical studies in which Sameer A. Parikh is a principal investigator. Honoraria has been provided to the institution from Pharmacyclics, Merck, AstraZeneca, Janssen, Genentech, Amgen, TG Therapeutics, Novalgen Limited, Kite Pharma, and AbbVie for Sameer A. Parikh’s participation in consulting activities/advisory board meetings. Research funding from: AbbVie, Acerta Pharma, Bristol Meyer Squib, Celgene, Genentech, MEI Pharma, Pharmacyclics, Sunesis, TG Therapeutics, Tolero Pharmaceuticals.