Coronavirus disease 2019 (COVID-19) vaccines effectively elicit humoral and cellular immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in healthy populations. This immunity decreases several months after vaccination. However, the efficacy of vaccine-induced immunity and its durability in patients with severe asthma on biological therapy are unknown. In this study, we evaluated the effectiveness and durability of mRNA vaccine-induced SARS-CoV-2-specific humoral and cellular immunity in severe asthma patients on biological therapy. The study included 34 patients with severe asthma treated with anti-IgE (omalizumab, n=17), anti-IL5 (mepolizumab, n=13; reslizumab, n=3), or anti-IL5R (benralizumab, n=1) biological therapy. All patients were vaccinated with two doses of the BNT162b2 mRNA vaccine with a 6-week interval between the doses. We found that this COVID-19 vaccination regimen elicited SARS-CoV-2-specific humoral and cellular immunity, which had significantly declined 6 months after receipt of the second dose of the vaccine. The type of biological treatment did not affect vaccine-elicited immunity. However, patient age negatively impacted the vaccine-induced humoral response. On the other hand, no such age-related impact on vaccine-elicited cellular immunity was observed. Our findings show that treatment of patients with severe asthma with biological therapy does not compromise the effectiveness or durability of COVID-19 vaccine-induced immunity.

Department of Immunology 2nd Faculty of Medicine Charles University and Motol University Hospital Prague Czechia

Department of Pediatrics 2nd Faculty of Medicine Charles University and Motol University Hospital Prague Czechia

Department of Pneumology 2nd Faculty of Medicine Charles University and Motol University Hospital Prague Czechia

Zobrazit více v PubMed

Khan WH, Hashmi Z, Goel A, Ahmad R, Gupta K, Khan N, et al. Covid-19 Pandemic and Vaccines Update on Challenges and Resolutions. Front Cell Infect Microbiol (2021) 11:690621. doi:  10.3389/fcimb.2021.690621 PubMed DOI PMC

Polack FP, Thomas SJ, Kitchin N, Absalon J, Gurtman A, Lockhart S, et al. Safety and Efficacy of the BNT162b2 Mrna Covid-19 Vaccine. N Engl J Med (2020) 383(27):2603–15. doi:  10.1056/NEJMoa2034577 PubMed DOI PMC

Baden LR, El Sahly HM, Essink B, Kotloff K, Frey S, Novak R, et al. Efficacy and Safety of the Mrna-1273 SARS-CoV-2 Vaccine. N Engl J Med (2021) 384(5):403–16. doi:  10.1056/NEJMoa2035389 PubMed DOI PMC

Dunkle LM, Kotloff KL, Gay CL, Anez G, Adelglass JM, Barrat Hernandez AQ, et al. Efficacy and Safety of NVX-CoV2373 in Adults in the United States and Mexico. N Engl J Med (2021) 386:531–43. doi:  10.1056/NEJMoa2116185 PubMed DOI PMC

Sadoff J, Gray G, Vandebosch A, Cardenas V, Shukarev G, Grinsztejn B, et al. Safety and Efficacy of Single-Dose Ad26.Cov2.s Vaccine Against Covid-19. N Engl J Med (2021) 384(23):2187–201. doi:  10.1056/NEJMoa2101544 PubMed DOI PMC

Voysey M, Clemens SAC, Madhi SA, Weckx LY, Folegatti PM, Aley PK, et al. Safety and Efficacy of the ChAdOx1 nCoV-19 Vaccine (AZD1222) Against SARS-CoV-2: An Interim Analysis of Four Randomised Controlled Trials in Brazil, South Africa, and the UK. Lancet (2021) 397(10269):99–111. doi:  10.1016/S0140-6736(20)32661-1 PubMed DOI PMC

Sahin U, Muik A, Derhovanessian E, Vogler I, Kranz LM, Vormehr M, et al. Covid-19 Vaccine BNT162b1 Elicits Human Antibody and TH1 T Cell Responses. Nature (2020) 586(7830):594–9. doi:  10.1038/s41586-020-2814-7 PubMed DOI

Kemp SA, Collier DA, Datir RP, Ferreira I, Gayed S, Jahun A, et al. Sars-CoV-2 Evolution During Treatment of Chronic Infection. Nature (2021) 592(7853):277–82. doi:  10.1038/s41586-021-03291-y PubMed DOI PMC

Khoury DS, Cromer D, Reynaldi A, Schlub TE, Wheatley AK, Juno JA, et al. Neutralizing Antibody Levels Are Highly Predictive of Immune Protection From Symptomatic SARS-CoV-2 Infection. Nat Med (2021) 27(7):1205–11. doi:  10.1038/s41591-021-01377-8 PubMed DOI

Deeks SG, Martin JN, Sinclair E, Harris J, Neilands TB, Maecker HT, et al. Strong Cell-Mediated Immune Responses Are Associated With the Maintenance of Low-Level Viremia in Antiretroviral-Treated Individuals With Drug-Resistant Human Immunodeficiency Virus Type 1. J Infect Dis (2004) 189(2):312–21. doi:  10.1086/380098 PubMed DOI

Mudd PA, Martins MA, Ericsen AJ, Tully DC, Power KA, Bean AT, et al. Vaccine-Induced CD8+ T Cells Control AIDS Virus Replication. Nature (2012) 491(7422):129–33. doi:  10.1038/nature11443 PubMed DOI PMC

Israelow B, Mao T, Klein J, Song E, Menasche B, Omer SB, et al. Adaptive Immune Determinants of Viral Clearance and Protection in Mouse Models of SARS-Cov-2. Sci Immunol (2021) 6(64):eabl4509. doi:  10.1126/sciimmunol.abl4509 PubMed DOI PMC

McMahan K, Yu J, Mercado NB, Loos C, Tostanoski LH, Chandrashekar A, et al. Correlates of Protection Against SARS-CoV-2 in Rhesus Macaques. Nature (2021) 590(7847):630–4. doi:  10.1038/s41586-020-03041-6 PubMed DOI PMC

Dolgin E. COVID Vaccine Immunity is Waning - How Much Does That Matter? Nature (2021) 597(7878):606–7. doi:  10.1038/d41586-021-02532-4 PubMed DOI

Goldberg Y, Mandel M, Bar-On YM, Bodenheimer O, Freedman L, Haas EJ, et al. Waning Immunity After the BNT162b2 Vaccine in Israel. N Engl J Med (2021) 385(24):e85. doi:  10.1056/NEJMoa2114228 PubMed DOI PMC

Levin EG, Lustig Y, Cohen C, Fluss R, Indenbaum V, Amit S, et al. Waning Immune Humoral Response to BNT162b2 Covid-19 Vaccine Over 6 Months. N Engl J Med (2021) 385:e84. doi:  10.1056/NEJMoa2114583 PubMed DOI PMC

Munro APS, Janani L, Cornelius V, Aley PK, Babbage G, Baxter D, et al. Safety and Immunogenicity of Seven COVID-19 Vaccines as a Third Dose (Booster) Following Two Doses of ChAdOx1 nCov-19 or BNT162b2 in the UK (Cov-BOOST): A Blinded, Multicentre, Randomised, Controlled, Phase 2 Trial. Lancet (2021) 398(10318):2258–76. doi:  10.1016/S0140-6736(21)02717-3 PubMed DOI PMC

Boyarsky BJ, Werbel WA, Avery RK, Tobian AAR, Massie AB, Segev DL, et al. Antibody Response to 2-Dose SARS-CoV-2 Mrna Vaccine Series in Solid Organ Transplant Recipients. JAMA (2021) 325(21):2204–6. doi:  10.1001/jama.2021.7489 PubMed DOI PMC

Marion O, Del Bello A, Abravanel F, Couat C, Faguer S, Esposito L, et al. Safety and Immunogenicity of Anti-SARS-CoV-2 Messenger RNA Vaccines in Recipients of Solid Organ Transplants. Ann Intern Med (2021) 174(9):1336–8. doi:  10.7326/M21-1341 PubMed DOI PMC

Becerril-Gaitan A, Vaca-Cartagena BF, Ferrigno AS, Mesa-Chavez F, Barrientos-Gutierrez T, Tagliamento M, et al. Immunogenicity and Risk of Severe Acute Respiratory Syndrome Coronavirus 2 (Sars-CoV-2) Infection After Coronavirus Disease 2019 (Covid-19) Vaccination in Patients With Cancer: A Systematic Review and Meta-Analysis. Eur J Cancer (2022) 160:243–60. doi:  10.1016/j.ejca.2021.10.014 PubMed DOI PMC

Chen JJ, Lee TH, Tian YC, Lee CC, Fan PC, Chang CH. Immunogenicity Rates After SARS-CoV-2 Vaccination in People With End-stage Kidney Disease: A Systematic Review and Meta-Analysis. JAMA Netw Open (2021) 4(10):e2131749. doi:  10.1001/jamanetworkopen.2021.31749 PubMed DOI PMC

Haberman RH, Herati R, Simon D, Samanovic M, Blank RB, Tuen M, et al. Methotrexate Hampers Immunogenicity to BNT162b2 Mrna COVID-19 Vaccine in Immune-Mediated Inflammatory Disease. Ann Rheum Dis (2021) 80(10):1339–44. doi:  10.1136/annrheumdis-2021-220597 PubMed DOI PMC

Yang JM, Koh HY, Moon SY, Yoo IK, Ha EK, You S, et al. Allergic Disorders and Susceptibility to and Severity of COVID-19: A Nationwide Cohort Study. J Allergy Clin Immunol (2020) 146(4):790–8. doi:  10.1016/j.jaci.2020.08.008 PubMed DOI PMC

Zhu Z, Hasegawa K, Ma B, Fujiogi M, Camargo CA, Jr, Liang L. Association of Asthma and Its Genetic Predisposition With the Risk of Severe COVID-19. J Allergy Clin Immunol (2020) 146 327-329(2):e324. doi:  10.1016/j.jaci.2020.06.001 PubMed DOI PMC

Chhiba KD, Patel GB, Vu THT, Chen MM, Guo A, Kudlaty E, et al. Prevalence and Characterization of Asthma in Hospitalized and Nonhospitalized Patients With COVID-19. J Allergy Clin Immunol (2020) 146 307-314(2):e304. doi:  10.1016/j.jaci.2020.06.010 PubMed DOI PMC

Lovinsky-Desir S, Deshpande DR, De A, Murray L, Stingone JA, Chan A, et al. Asthma Among Hospitalized Patients With COVID-19 and Related Outcomes. J Allergy Clin Immunol (2020) 146 1027-1034(5):e1024. doi:  10.1016/j.jaci.2020.07.026 PubMed DOI PMC

Robinson LB, Fu X, Bassett IV, Triant VA, Foulkes AS, Zhang Y, et al. Covid-19 Severity in Hospitalized Patients With Asthma: A Matched Cohort Study. J Allergy Clin Immunol Pract (2021) 9(1):497–500. doi:  10.1016/j.jaip.2020.10.021 PubMed DOI PMC

Lombardi C, Gani F, Berti A, Comberiati P, Peroni D, Cottini M. Asthma and COVID-19: A Dangerous Liaison? Asthma Res Pract (2021) 7(1):9. doi:  10.1186/s40733-021-00075-z PubMed DOI PMC

Caminati M, Guarnieri G, Batani V, Scarpieri E, Finocchiaro A, Chieco-Bianchi F, et al. Covid-19 Vaccination in Patients With Severe Asthma on Biologic Treatment: Safety, Tolerability, and Impact on Disease Control. Vaccines (Basel) (2021) 9(8):1–8. doi:  10.3390/vaccines9080853 PubMed DOI PMC

Rodrigo GJ, Neffen H, Castro-Rodriguez JA. Efficacy and Safety of Subcutaneous Omalizumab vs Placebo as Add-on Therapy to Corticosteroids for Children and Adults With Asthma: A Systematic Review. Chest (2011) 139(1):28–35. doi:  10.1378/chest.10-1194 PubMed DOI

Edris A, De Feyter S, Maes T, Joos G, Lahousse L. Monoclonal Antibodies in Type 2 Asthma: A Systematic Review and Network Meta-Analysis. Respir Res (2019) 20(1):179. doi:  10.1186/s12931-019-1138-3 PubMed DOI PMC

Taborska P, Bartunkova J, Smrz D. Simultaneous PubMed DOI

Taborska P, Lastovicka J, Stakheev D, Strizova Z, Bartunkova J, Smrz D. Sars-CoV-2 Spike Glycoprotein-Reactive T Cells can be Readily Expanded From COVID-19 Vaccinated Donors. Immun Inflammation Dis (2021) 9(4):1452–67. doi:  10.1002/iid3.496 PubMed DOI PMC

Reddel HK, FitzGerald JM, Bateman ED, Bacharier LB, Becker A, Brusselle G, et al. GINA 2019: A Fundamental Change in Asthma Management: Treatment of Asthma With Short-Acting Bronchodilators Alone is No Longer Recommended for Adults and Adolescents. Eur Respir J (2019) 53(6):1–7. doi:  10.1183/13993003.01046-2019 PubMed DOI

Reddel HK, Bacharier LB, Bateman ED, Brightling CE, Brusselle GG, Buhl R, et al. Global Initiative for Asthma (Gina) Strategy 2021 - Executive Summary and Rationale for Key Changes. J Allergy Clin Immunol Pract (2021) 10(1):S1–S18. doi:  10.1016/j.jaip.2021.10.001 PubMed DOI

Smits VAJ, Hernandez-Carralero E, Paz-Cabrera MC, Cabrera E, Hernandez-Reyes Y, Hernandez-Fernaud JR, et al. The Nucleocapsid Protein Triggers the Main Humoral Immune Response in COVID-19 Patients. Biochem Biophys Res Commun (2021) 543:45–9. doi:  10.1016/j.bbrc.2021.01.073 PubMed DOI PMC

Galipeau Y, Siragam V, Laroche G, Marion E, Greig M, McGuinty M, et al. Relative Ratios of Human Seasonal Coronavirus Antibodies Predict the Efficiency of Cross-Neutralization of SARS-CoV-2 Spike Binding to ACE2. EBioMedicine (2021) 74:103700. doi:  10.1016/j.ebiom.2021.103700 PubMed DOI PMC

Altmann DM, Boyton RJ. SARS-Cov-2 T Cell Immunity: Specificity, Function, Durability, and Role in Protection. Sci Immunol (2020) 5(49), 1–5. doi:  10.1126/sciimmunol.abd6160 PubMed DOI

Rosenberg ES, Billingsley JM, Caliendo AM, Boswell SL, Sax PE, Kalams SA, et al. Vigorous HIV-1-specific Cd4+ T Cell Responses Associated With Control of Viremia. Science (1997) 278(5342):1447–50. doi:  10.1126/science.278.5342.1447 PubMed DOI

Combadiere B, Boissonnas A, Carcelain G, Lefranc E, Samri A, Bricaire F, et al. Distinct Time Effects of Vaccination on Long-Term Proliferative and IFN-Gamma-Producing T Cell Memory to Smallpox in Humans. J Exp Med (2004) 199(11):1585–93. doi:  10.1084/jem.20032083 PubMed DOI PMC

Oberhardt V, Luxenburger H, Kemming J, Schulien I, Ciminski K, Giese S, et al. Rapid and Stable Mobilization of CD8(+) T Cells by SARS-CoV-2 mRNA Vaccine. Nature (2021) 597(7875):268–73. doi:  10.1038/s41586-021-03841-4 PubMed DOI PMC

Taborska P, Strizova Z, Stakheev D, Sojka L, Bartunkova J, Smrz D. Cd4(+) T Cells of Prostate Cancer Patients Have Decreased Immune Responses to Antigens Derived From SARS-Cov-2 Spike Glycoprotein. Front Immunol (2021) 12:629102. doi:  10.3389/fimmu.2021.629102 PubMed DOI PMC

Brusselle GG, Koppelman GH. Biologic Therapies for Severe Asthma. N Engl J Med (2022) 386(2):157–71. doi:  10.1056/NEJMra2032506 PubMed DOI

Esquivel A, Busse WW, Calatroni A, Togias AG, Grindle KG, Bochkov YA, et al. Effects of Omalizumab on Rhinovirus Infections, Illnesses, and Exacerbations of Asthma. Am J Respir Crit Care Med (2017) 196(8):985–92. doi:  10.1164/rccm.201701-0120OC PubMed DOI PMC

Rowe RK, Pyle DM, Tomlinson AR, Lv T, Hu Z, Gill MA. Ige Cross-Linking Impairs Monocyte Antiviral Responses and Inhibits Influenza-Driven TH1 Differentiation. J Allergy Clin Immunol (2017) 140(1):294–298 e298. doi:  10.1016/j.jaci.2016.11.035 PubMed DOI PMC

Farmani AR, Mahdavinezhad F, Moslemi R, Mehrabi Z, Noori A, Kouhestani M, et al. Anti-IgE Monoclonal Antibodies as Potential Treatment in COVID-19. Immunopharmacol Immunotoxicol (2021) 43(3):259–64. doi:  10.1080/08923973.2021.1925906 PubMed DOI PMC

Sabogal Pineros YS, Bal SM, van de Pol MA, Dierdorp BS, Dekker T, Dijkhuis A, et al. Anti-IL-5 in Mild Asthma Alters Rhinovirus-Induced Macrophage, B-Cell, and Neutrophil Responses (Material). A Placebo-Controlled, Double-Blind Study. Am J Respir Crit Care Med (2019) 199(4):508–17. doi:  10.1164/rccm.201803-0461OC PubMed DOI

Castro M, Zangrilli J, Wechsler ME, Bateman ED, Brusselle GG, Bardin P, et al. Reslizumab for Inadequately Controlled Asthma With Elevated Blood Eosinophil Counts: Results From Two Multicentre, Parallel, Double-Blind, Randomised, Placebo-Controlled, Phase 3 Trials. Lancet Respir Med (2015) 3(5):355–66. doi:  10.1016/S2213-2600(15)00042-9 PubMed DOI

Jackson DJ, Korn S, Mathur SK, Barker P, Meka VG, Martin UJ, et al. Safety of Eosinophil-Depleting Therapy for Severe, Eosinophilic Asthma: Focus on Benralizumab. Drug Saf (2020) 43(5):409–25. doi:  10.1007/s40264-020-00926-3 PubMed DOI PMC

Poddighe D, Kovzel E. Impact of Anti-Type 2 Inflammation Biologic Therapy on COVID-19 Clinical Course and Outcome. J Inflamm Res (2021) 14:6845–53. doi:  10.2147/JIR.S345665 PubMed DOI PMC

Havlin J, Skotnicova A, Dvorackova E, Hubacek P, Svorcova M, Lastovicka J, et al. Impaired Humoral Response to Third Dose of BNT162b2 Mrna COVID-19 Vaccine Despite Detectable Spike Protein-Specific T Cells in Lung Transplant Recipients. Transplantation (2021) 106(3):e183–4. doi:  10.1097/TP.0000000000004021 PubMed DOI PMC

Havlin J, Svorcova M, Dvorackova E, Lastovicka J, Lischke R, Kalina T, et al. Immunogenicity of BNT162b2 Mrna COVID-19 Vaccine and SARS-CoV-2 Infection in Lung Transplant Recipients. J Heart Lung Transplant (2021) 40(8):754–8. doi:  10.1016/j.healun.2021.05.004 PubMed DOI PMC

Lee A, Wong SY, Chai LYA, Lee SC, Lee MX, Muthiah MD, et al. Efficacy of covid-19 Vaccines in Immunocompromised Patients: Systematic Review and Meta-Analysis. BMJ (2022) 376:e068632. doi:  10.1136/bmj-2021-068632 PubMed DOI PMC

Naaber P, Tserel L, Kangro K, Sepp E, Jurjenson V, Adamson A, et al. Dynamics of Antibody Response to BNT162b2 Vaccine After Six Months: A Longitudinal Prospective Study. Lancet Reg Health Eur (2021) 10:100208. doi:  10.1016/j.lanepe.2021.100208 PubMed DOI PMC

Guerrera G, Picozza M, D’Orso S, Placido R, Pirronello M, Verdiani A, et al. BNT162b2 Vaccination Induces Durable SARS-Cov-2-Specific T Cells With a Stem Cell Memory Phenotype. Sci Immunol (2021) 6(66):eabl5344. doi:  10.1126/sciimmunol.abl5344 PubMed DOI

Collier DA, Ferreira I, Kotagiri P, Datir RP, Lim EY, Touizer E, et al. Age-Related Immune Response Heterogeneity to SARS-CoV-2 Vaccine BNT162b2. Nature (2021) 596(7872):417–22. doi:  10.1038/s41586-021-03739-1 PubMed DOI PMC

Muller L, Andree M, Moskorz W, Drexler I, Walotka L, Grothmann R, et al. Age-Dependent Immune Response to the Biontech/Pfizer Bnt162b2 Coronavirus Disease 2019 Vaccination. Clin Infect Dis (2021) 73(11):2065–72. doi:  10.1093/cid/ciab381 PubMed DOI PMC

Romero-Olmedo AJ, Schulz AR, Hochstatter S, Das Gupta D, Virta I, Hirseland H, et al. Induction of Robust Cellular and Humoral Immunity Against SARS-CoV-2 After a Third Dose of BNT162b2 Vaccine in Previously Unresponsive Older Adults. Nat Microbiol (2022). doi:  10.1038/s41564-021-01046-z PubMed DOI