Antibody binding and neutralization of live SARS-CoV-2 variants including BA.4/5 following booster vaccination of patients with B-cell malignancies.

Non-Hodgkin lymphoma and chronic lymphocytic leukemia (NHL/CLL) patients elicit inadequate antibody responses after initial SARS-CoV-2 vaccination and remain at high risk of severe COVID-19 disease. We investigated IgG, IgA, and IgM responses after booster vaccination against recent SARS-CoV-2 variants including Omicron BA.5 in 67 patients. Patients had lower fold increase and total anti-spike binding titers after booster than healthy individuals. Antibody responses negatively correlated with recent anti-CD20 therapy and low B cell numbers. Antibodies generated after booster demonstrated similar binding properties against SARS-CoV-2 variants compared to those generated by healthy controls with lower binding against Omicron variants. Importantly, 43% of patients showed anti-Omicron BA.1 neutralizing antibodies after booster and all these patients also had anti-Omicron BA.5 neutralizing antibodies. NHL/CLL patients demonstrated inferior antibody responses after booster vaccination, particularly against Omicron variants. Prioritization of prophylactic and treatment agents and vaccination of patients and close contacts with updated vaccine formulations are essential.
Competing Interests: Conflict of Interest Statement Victor M. Orellana-Noia Consulting or Advisory Role: ADC TherapeuticsUncompensated Relationships: Roche/Genentech Kristie A. Blum Honoraria: American Society of Hematology, Leidos Biomedical Research/NCIResearch Funding: Genentech/Roche (Inst), Seattle Genetics (Inst), BMSi (Inst)Travel, Accommodations, Expenses: American Society of Hematology Pamela B. Allen Consulting or Advisory Role: ADC therapeutics, Epizyme, Kyowa Kirin, Daichii Sankyo, Secura Bio. Mary Jo Lechowicz Consulting or Advisory Role: Kyowa Kirin, Secura Bio, EUSA Pharma Ajay K. Nooka Honoraria: Amgen, Janssen Oncology, Bristol Myers Squibb/Celgene, GlaxoSmithKline, Takeda, Oncopeptides, Karyopharm Therapeutics, Adaptive Biotechnologies, Genzyme, BeyondSpring Pharmaceuticals, Secura BioConsulting or Advisory Role: Amgen, Janssen Oncology, Bristol Myers Squibb, GlaxoSmithKline, Takeda, Oncopeptides, Karyopharm Therapeutics, Adaptive Biotechnologies, Genzyme, BeyondSpring Pharmaceuticals, Secura BioResearch Funding: Amgen (Inst), Janssen Oncology (Inst), Takeda (Inst), Bristol Myers Squibb/Celgene (Inst), Arch Oncology (Inst), GlaxoSmithKline (Inst)Travel, Accommodations, Expenses: GlaxoSmithKline Jean L. Koff Consulting or Advisory Role: Janssen/Pharmacyclics, MorphoSys, TG Therapeutics, Gamida CellResearch Funding: Celgene, Janssen/Pharmacyclics, Oncternal Therapeutics, Viracta Therapeutics, Atara Biotherapeutics Madhav V. Dhodapkar Consulting or Advisory Role: Roche/Genentech, Amgen, Kite, a Gilead company, lava therapeutics, Janssen Oncology, Celgene Mehul S. Suthar Consulting or Advisory Role: Moderna Therapeutics, OcugenResearch Funding: Moderna Therapeutics (Inst), Ocugen (Inst) Jonathon B. Cohen Consulting or Advisory Role: AbbVie, Janssen, Loxo, Kite/Gilead, AstraZeneca, Aptitude Medical, Adicet Bio, Adaptive BiotechnologiesResearch Funding: Bristol Myers Squibb (Inst), Janssen (Inst), Novartis (Inst), Takeda (Inst), AI Therapeutics (Inst), Genentech (Inst), ASH (Inst), Lymphoma Research Foundation (Inst), Loxo (Inst), Bioinvent (Inst), AstraZeneca (Inst) Rafi Ahmed Research Funding: MerckPatents, Royalties, Other Intellectual Property: Patents on PD-1–directed immunotherapy; I am listed as a coinventor on an Emory University held patent for SARS-CoV-2 serology assays The remaining authors have no conflicts to declare.