Patients taking benralizumab, dupilumab, or mepolizumab have lower postvaccination SARS-CoV-2 immunity - 13/06/24

Doi : 10.1016/j.jaci.2024.03.029

Martin C. Runnstrom, MD ^a,^b,^{^{∗
These authors contributed equally to this work.}}, Pedro A. Lamothe, MD, PhD ^a,^{^{∗
These authors contributed equally to this work.}}, Caterina E. Faliti, PharmD, PhD ^c,^d, Narayanaiah Cheedarla, PhD ^e, Alberto Moreno, MD ^f,^g, Mehul S. Suthar, PhD ^h,ⁱ, Rishika Nahata, BS ^j, Mayuran Ravindran, MD ^k, Natalie S. Haddad, MS ^a, Andrea Morrison-Porter, BS ^a, Hannah Quehl, BS ^a, Richard P. Ramonell, MD ^l, Matthew Woodruff, PhD ^c,^d, Fabliha Anam, BS ^c,^d, Rebeca Zhang, MS ^m, Colin Swenson, MD ^a, Carmen Polito, MD ^a, Wendy Neveu, MD ^a, Rahulkumar Patel, MD ^a, Natalia Smirnova, MD ^a, Doan C. Nguyen, PhD, MD ^a,^d, Caroline Kim, BS ^a, Ian Hentenaar, BS ^a, Shuya Kyu, MS ^a, Sabeena Usman, BS ^a, Thuy Ngo, BS ^a, Zhenxing Guo, PhD ^m, Hao Wu, PhD ^m, John L. Daiss, PhD ^a, Jiwon Park, BS ^a, Kelly E. Manning, BS ^h,ⁱ, Bursha Wali, PhD ^h,ⁱ, Madison L. Ellis, BS ^h,ⁱ, Sunita Sharma, MD ⁿ, Fernando Holguin, MD ⁿ, Suneethamma Cheedarla, BS ^e, Andrew S. Neish, MD ^e, John D. Roback, MD, PhD ^e, Ignacio Sanz, MD ^c,^d, F. Eun-Hyung Lee, MD ^a,^⁎
^a Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Medicine, Emory University School of Medicine, Atlanta, Ga
^b Department of Medicine, Atlanta Veterans Affairs Healthcare System, Atlanta, Ga
^c Division of Rheumatology, Department of Medicine, Emory University School of Medicine, Atlanta, Ga
^d Lowance Center for Human Immunology, Atlanta, Ga
^e Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Ga
^f Division of Infectious Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, Ga
^g Yerkes National Primate Research Center, Atlanta, Ga
^h Emory Vaccine Center, Emory University School of Medicine, Atlanta, Ga
ⁱ Center for Childhood Infections and Vaccines of Children’s Healthcare of Atlanta, Department of Pediatrics, Emory University School of Medicine, Atlanta, Ga
^j Emory College of Arts and Sciences, Emory University, Atlanta, Ga
^k J. Willis Hurst Internal Medicine Residency Program, Emory University School of Medicine, Atlanta, Ga
^l Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pa
^m Department of Biostatistics and Bioinformatics, Emory University, Atlanta, Ga
ⁿ Division of Pulmonary Sciences and Critical Care Medicine, Department of Medicine, University of Colorado, Denver, Colo

^∗Corresponding author: Frances Eun-Hyung Lee, MD, 615 Michael St, NE Suite 205, Atlanta, GA 30322.615 Michael StNE Suite 205AtlantaGA30322

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Abstract

Background

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.

Objective

Our aim was to evaluate the antibody and cellular immunity after SARS-CoV-2 mRNA vaccination in patients on biologics (PoBs).

Methods

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.

Results

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.

Conclusion

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.

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Key words : Asthma biologics, SARS-CoV-2, COVID-19, mRNA vaccines, benralizumab, dupilumab, mepolizumab, antibody neutralization, memory B cells, memory T cells

Abbreviations used : ACE-2, AIM, ASC, BM, COVID-19, DN, GC, IHC, MFI, NB, PoB, PC, RBD, SARS-CoV-2, T_FH, WT