Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023 Feb:135:102981.
doi: 10.1016/j.jaut.2022.102981. Epub 2022 Dec 22.

Accelerated waning of immune responses to a third COVID-19 vaccination in patients with immune-mediated inflammatory diseases

Daniel Mrak  1 , Felix Kartnig  1 , Daniela Sieghart  1 , Elisabeth Simader  1 , Helga Radner  1 , Peter Mandl  1 , Lisa Göschl  1 , Philipp Hofer  2 , Thomas Deimel  1 , Irina Gessl  1 , Renate Kain  2 , Stefan Winkler  3 , Josef S Smolen  1 , Thomas Perkmann  4 , Helmuth Haslacher  4 , Daniel Aletaha  1 , Leonhard X Heinz  5 , Michael Bonelli  6
Affiliations

Accelerated waning of immune responses to a third COVID-19 vaccination in patients with immune-mediated inflammatory diseases

Daniel Mrak et al. J Autoimmun. 2023 Feb.

Abstract

Background: A 3rd COVID-19 vaccination is currently recommended for patients under immunosuppression. However, a fast decline of antibodies against the SARS-CoV-2 receptor-binding domain (RBD) of the spike protein has been observed. Currently it remains unclear whether immunosuppressive therapy affects kinetics of humoral and cellular immune responses.

Methods: 50 patients under immunosuppression and 42 healthy controls (HCs) received a 3rd dose of an mRNA-based vaccine and were monitored over a 12-weeks period. Humoral immune response was assessed 4 and 12 weeks after 3rd dose. Antibodies were quantified using the Elecsys Anti-SARS-CoV-2 Spike immunoassay against the receptor-binding domain (RBD) of the spike protein. SARS-CoV-2-specific T cell responses were quantified by IFN-γ ELISpot assays. Adverse events, including SARS-CoV-2 infections, were monitored over a 12-week period.

Results: At week 12, reduced anti-RBD antibody levels were observed in IMID patients as compared to HCs (median antibody level 5345 BAU/ml [1781-10,208] versus 9650 BAU/ml [6633-16,050], p < 0.001). Reduction in relative antibody levels was significantly higher in IMID patients as compared to HCs at week 12 (p < 0.001). Lowest anti-RBD antibody levels were detected in IMID patients who received biological disease-modifying anti-rheumatic drugs (DMARDs) or a combination therapy with conventional synthetic and biological DMARDs. Number of SARS-CoV-2-specific T cells against wildtype and Omicron variants remained stable over 12 weeks in IMID patients. No serious adverse events were reported.

Conclusion: Due to a fast decline in anti-RBD antibodies in IMID patients an early 4th vaccination should be considered in this vulnerable group of patients.

Keywords: COVID-19; Immunosuppression; SARS-CoV-2; Vaccination.

PubMed Disclaimer

Conflict of interest statement

Declaration of competing interest DM reports support for meeting attendances from Pfizer and consultation fees from AstraZeneca; JS reports about grants, consulting and personal fees from AbbVie, Amgen, AstraZeneca, Astro, Bristol-Myers Squibb, Celltrion, Gilead-Galapagos, Janssen, Lilly, Pfizer, R-Pharma, Samsung, Sanofi, Chugai, Merck Sharp & Dohme, Novartis-Sandoz Roche, Samsung and UCB and grants from Abbvie, AstraZeneca, Lilly, Novartis, and Roche; HR received speaker fees from Gilead, Merck Sharp and Pfizer and travel support from Janssen; HH received grants from Glock Health, BlueSky Immunotherapies and Neutrolis; DA received grants, speaker fees, or consultancy fees from Abbvie, Amgen, Galapagos, Lilly, Janssen, Merck, Novartis, Pfizer, Sandoz, and Sanofi; RK reports consulting fees from AstraZeneca, Takeda Pharma, MEDahead and Janssen Cilag and speaker fees from Otsuka; ES received travel support from Pfizer, Bristol-Myers Squibb and Boehringer-Ingelheim and speaker fees from Lilly; MB reports about personal fees from Eli-Lilly. All other authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Trial flow diagram.
Fig. 2
Fig. 2
Humoral immune response at week 4 after 3rdvaccination. A) Antibody levels to the receptor-binding domain (RBD) of the viral spike (S) protein in patients (n = 50) and healthy controls (n = 42) at screening (week 0), week 4 and week 12 after the 3rd vaccination. B) Relative anti-RBD antibody abundance at week 12 (week 4 = 100%) in patients and HCs.
Fig. 3
Fig. 3
SARS-CoV-2-specific T-cell response. SARS-CoV-2-specific T-cell responses were determined by ELISpot assay from peripheral blood mononuclear cells (PBMCs) stimulated with wild type (WT) and Omicron spike subunit S1 and S2 peptide pools at week 0, 1 and 12 after the 3rd vaccination. A) Ex vivo IFN-γ ELISpot results of 28 patients and 25 HCs for SARS-CoV-2 WT and Omicron peptide pools at week 0, week 1 and week 12 post vaccination. B) Correlation of average SFCs/106 PBMCs for Omicron peptide pools at week 1 with antibody levels to the receptor-binding domain (RBD) of the viral spike (S) protein at week 4 and 12 post vaccination.
Fig. 4
Fig. 4
Treatment-specific response to a 3rdvaccination. A) Antibody levels to the receptor-binding domain (RBD) of the viral spike (S) protein at week 0, 4 and 12 in HCs (42), patients with csDMARD (25), bDMARD (14) or csDMARD/bDMARD combination treatment (10). B) Relative anti-RBD antibody abundance at week 12 (week 4 = 100%) in patients and HCs for the indicated treatments.
See this image and copyright information in PMC

References

    1. Sette A., Crotty S. Adaptive immunity to SARS-CoV-2 and COVID-19. Cell. 2021;184:861–880. doi: 10.1016/j.cell.2021.01.007. - DOI - PMC - PubMed
    1. Furer V., Eviatar T., Zisman D., Peleg H., Paran D., Levartovsky D., Zisapel M., Elalouf O., Kaufman I., Meidan R., Broyde A., Polachek A., Wollman J., Litinsky I., Meridor K., Nochomovitz H., Silberman A., Rosenberg D., Feld J., Haddad A., Gazzit T., Elias M., Higazi N., Kharouf F., Shefer G., Sharon O., Pel S., Nevo S., Elkayam O. Immunogenicity and safety of the BNT162b2 mRNA COVID-19 vaccine in adult patients with autoimmune inflammatory rheumatic diseases and in the general population: a multicentre study. Ann. Rheum. Dis. 2021;80:1330–1338. doi: 10.1136/annrheumdis-2021-220647. - DOI - PubMed
    1. Wieske L., van Dam K.P.J., Steenhuis M., Stalman E.W., Kummer L.Y.L., van Kempen Z.L.E., Killestein J., Volkers A.G., Tas S.W., Boekel L., Wolbink G.J., van der Kooi A.J., Raaphorst J., Löwenberg M., Takkenberg R.B., D'Haens G.R.A.M., Spuls P.I., Bekkenk M.W., Musters A.H., Post N.F., Bosma A.L., Hilhorst M.L., Vegting Y., Bemelman F.J., Voskuyl A.E., Broens B., Sanchez A.P., van Els C.A.C.M., de Wit J., Rutgers A., de Leeuw K., Horváth B., Verschuuren J.J.G.M., Ruiter A.M., van Ouwerkerk L., van der Woude D., Allaart R.C.F., Teng Y.K.O., van Paassen P., Busch M.H., Jallah P.B.P., Brusse E., van Doorn P.A., Baars A.E., Hijnen D.J., Schreurs C.R.G., van der Pol W.L., Goedee H.S., Keijzer S., Keijser J.B.D., Boogaard A., Cristianawati O., Ten Brinke A., Verstegen N.J.M., Zwinderman K.A.H., van Ham S.M., Kuijpers T.W., Rispens T., Eftimov F. T2B! Immunity against SARS-CoV-2 study group, Humoral responses after second and third SARS-CoV-2 vaccination in patients with immune-mediated inflammatory disorders on immunosuppressants: a cohort study. Lancet Rheumatol. 2022 doi: 10.1016/S2665-9913(22)00034-0. - DOI - PMC - PubMed
    1. Simon D., Tascilar K., Fagni F., Kleyer A., Krönke G., Meder C., Dietrich P., Orlemann T., Mößner J., Taubmann J., Mutlu M.Y., Knitza J., Kemenes S., Liphardt A.-M., Schönau V., Bohr D., Schuster L., Hartmann F., Minopoulou I., Leppkes M., Ramming A., Pachowsky M., Schuch F., Ronneberger M., Kleinert S., Hueber A.J., Manger K., Manger B., Atreya R., Berking C., Sticherling M., Neurath M.F., Schett G. Intensity and longevity of SARS-CoV-2 vaccination response in patients with immune-mediated inflammatory disease: a prospective cohort study. Lancet Rheumatol. 2022;4 doi: 10.1016/S2665-9913(22)00191-6. e614–e625. - DOI - PMC - PubMed
    1. Haberman R.H., Herati R., Simon D., Samanovic M., Blank R.B., Tuen M., Koralov S.B., Atreya R., Tascilar K., Allen J.R., Castillo R., Cornelius A.R., Rackoff P., Solomon G., Adhikari S., Azar N., Rosenthal P., Izmirly P., Samuels J., Golden B., Reddy S.M., Neurath M.F., Abramson S.B., Schett G., Mulligan M.J., Scher J.U. Methotrexate hampers immunogenicity to BNT162b2 mRNA COVID-19 vaccine in immune-mediated inflammatory disease. Ann. Rheum. Dis. 2021;80:1339–1344. doi: 10.1136/annrheumdis-2021-220597. - DOI - PMC - PubMed

Publication types

Supplementary concepts