Patients taking benralizumab, dupilumab, or mepolizumab have lower postvaccination SARS-CoV-2 immunity

• Published in: Journal of allergy and clinical immunology Vol. 154; no. 2; pp. 435 - 446
• Main Authors: Runnstrom, Martin C., Lamothe, Pedro A., Faliti, Caterina E., Cheedarla, Narayanaiah, Moreno, Alberto, Suthar, Mehul S., Nahata, Rishika, Ravindran, Mayuran, Haddad, Natalie S., Morrison-Porter, Andrea, Quehl, Hannah, Ramonell, Richard P., Woodruff, Matthew, Anam, Fabliha, Zhang, Rebeca, Swenson, Colin, Polito, Carmen, Neveu, Wendy, Patel, Rahulkumar, Smirnova, Natalia, Nguyen, Doan C., Kim, Caroline, Hentenaar, Ian, Kyu, Shuya, Usman, Sabeena, Ngo, Thuy, Guo, Zhenxing, Wu, Hao, Daiss, John L., Park, Jiwon, Manning, Kelly E., Wali, Bursha, Ellis, Madison L., Sharma, Sunita, Holguin, Fernando, Cheedarla, Suneethamma, Neish, Andrew S., Roback, John D., Sanz, Ignacio, Eun-Hyung Lee, F.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.08.2024
• Subjects: Adult; Aged; Antibodies, Monoclonal, Humanized - administration & dosage; Antibodies, Monoclonal, Humanized - therapeutic use; Antibodies, Viral - blood; Antibodies, Viral - immunology; antibody neutralization; Asthma - drug therapy; Asthma - immunology; Asthma biologics; benralizumab; COVID-19; COVID-19 - immunology; COVID-19 - prevention & control; COVID-19 Vaccines - administration & dosage; COVID-19 Vaccines - immunology; Dermatitis, Atopic - drug therapy; Dermatitis, Atopic - immunology; dupilumab; Female; Humans; Interleukin-5 - antagonists & inhibitors; Interleukin-5 - immunology; Male; memory B cells; memory T cells; mepolizumab; Middle Aged; mRNA vaccines; Prospective Studies; SARS-CoV-2; SARS-CoV-2 - immunology; Vaccination; PoB; AIM; IHC; mRNA vaccines; DN; BM; memory B cells; benralizumab; memory T cells; dupilumab; COVID-19; Asthma biologics; ASC; MFI; SARS-CoV-2; PC; NB; RBD; mepolizumab; TFH; antibody neutralization; ACE-2; GC; WT
• ISSN: 0091-6749; 1097-6825; 1097-6825
• DOI: 10.1016/j.jaci.2024.03.029

Biologic therapies inhibiting the IL-4 or IL-5 pathways are very effective in the treatment of asthma and other related conditions. However, the cytokines IL-4 and IL-5 also play a role in the generation of adaptive immune responses. Although these biologics do not cause overt immunosuppression, their effect in primary severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunization has not been studied completely. Our aim was to evaluate the antibody and cellular immunity after SARS-CoV-2 mRNA vaccination in patients on biologics (PoBs). Patients with severe asthma or atopic dermatitis who were taking benralizumab, dupilumab, or mepolizumab and had received the initial dose of the 2-dose adult SARS-CoV-2 mRNA vaccine were enrolled in a prospective, observational study. As our control group, we used a cohort of immunologically healthy subjects (with no significant immunosuppression) who were not taking biologics (NBs). We used a multiplexed immunoassay to measure antibody levels, neutralization assays to assess antibody function, and flow cytometry to quantitate Spike-specific lymphocytes. We analyzed blood from 57 patients in the PoB group and 46 control subjects from the NB group. The patients in the PoB group had lower levels of SARS-CoV-2 antibodies, pseudovirus neutralization, live virus neutralization, and frequencies of Spike-specific B and CD8 T cells at 6 months after vaccination. In subgroup analyses, patients with asthma who were taking biologics had significantly lower pseudovirus neutralization than did subjects with asthma who were not taking biologics. The patients in the PoB group had reduced SARS-CoV-2–specific antibody titers, neutralizing activity, and virus-specific B- and CD8 T-cell counts. These results have implications when considering development of a more individualized immunization strategy in patients who receive biologic medications blocking IL-4 or IL-5 pathways.