Skip to main content
Top
Published in: Clinical Rheumatology 5/2019

01-05-2019 | Influenza Vaccination | Original Article

The immunogenicity of seasonal and pandemic influenza vaccination in autoimmune inflammatory rheumatic patients—a 6-month follow-up prospective study

Authors: K. Lakota, K. Perdan-Pirkmajer, S. Sodin-Šemrl, S. Čučnik, V. Šubelj, K. Prosenc, K. Mrak Poljšak, M. Tomšič, A. Ambrožič, S. Praprotnik

Published in: Clinical Rheumatology | Issue 5/2019

Login to get access

Abstract

Introduction

Influenza may cause severe complications in patients with autoimmune inflammatory rheumatic disease (AIRD), to whom vaccinations are especially recommended. However, AIRD patients require cautious scrutiny of immunogenicity as they might exhibit poor antibody response to vaccination, especially when taking immunomodulatory medications.

Aim

The aim was to determine immunogenicity of seasonal and pandemic influenza vaccine in AIRD patients, its timeline/persistence, and influence of medications on immune response.

Methods

One hundred and thirty-seven AIRD and 54 healthy controls were vaccinated with trivalent seasonal influenza. After 3–5 weeks, 15 healthy controls and 93 AIRD were vaccinated with pandemic influenza vaccine, and 63 of patients were vaccinated a second time after 3–5 weeks. Sera were collected before vaccination, 18–90 days after each vaccination, and more than 180 days after the last vaccination. The immune response was measured using hemagglutination inhibition (HI) assay and IgG/IgA antibodies against influenza A/B with ELISA.

Results

Our findings indicate that following vaccination with seasonal influenza vaccine, seroprotection, seroresponse, and change in geometric mean titers (GMT) in AIRD patients was not compromised compared to healthy. Similarly, we report for pandemic influenza vaccination little added benefit of the second dose. We confirm lowest increase in HI titer in rituximab-treated AIRD compared to other medications. Vaccination largely tilts the balance from negative ELISA A IgG and IgA titers to positive titers in seasonal H1N1 seroresponsive AIRD patients and controls. A significant decrease in HI GMT and seroprotection was observed only in AIRD at > 180 days after vaccination highlighting an absent persistence of immunogenic response in AIRD patients. Due to high initial HI titers for influenza vaccine, we foresee their benefit in personalized medicine in the future.

Conclusion

Influenza vaccination is immunologically active for AIRD, with little value of the second dose of the pandemic vaccine and further scrutiny on persistence of immune response to vaccine in AIRD is needed.
Appendix
Available only for authorised users
Literature
3.
go back to reference Mereckiene J, Cotter S, Nicoll A, Lopalco P, Noori T, Weber JT, D’Ancona F, Lévy-Bruhl D, Dematte L, Giambi C, Valentiner-Branth P, Stankiewicz I, Appelgren E, O’Flanagan D (2014) Seasonal influenza immunisation in Europe. overview of recommendations and vaccination coverage for three seasons: pre-pandemic (2008/09), pandemic (2009/10) and post-pandemic (2010/11). Eurosurveillance 19(16). https://doi.org/10.2807/1560-7917.ES2014.19.16.20780 Mereckiene J, Cotter S, Nicoll A, Lopalco P, Noori T, Weber JT, D’Ancona F, Lévy-Bruhl D, Dematte L, Giambi C, Valentiner-Branth P, Stankiewicz I, Appelgren E, O’Flanagan D (2014) Seasonal influenza immunisation in Europe. overview of recommendations and vaccination coverage for three seasons: pre-pandemic (2008/09), pandemic (2009/10) and post-pandemic (2010/11). Eurosurveillance 19(16). https://​doi.​org/​10.​2807/​1560-7917.​ES2014.​19.​16.​20780
5.
go back to reference Atzeni F, Bendtzen K, Bobbio-Pallavicini F, Conti F, Cutolo M, Montecucco C, Sulli A, Valesini G, Sarzi-Puttini P (2008) Infections and treatment of patients with rheumatic diseases. Clin Exp Rheumatol 26(1 Suppl 48):S67–S73PubMed Atzeni F, Bendtzen K, Bobbio-Pallavicini F, Conti F, Cutolo M, Montecucco C, Sulli A, Valesini G, Sarzi-Puttini P (2008) Infections and treatment of patients with rheumatic diseases. Clin Exp Rheumatol 26(1 Suppl 48):S67–S73PubMed
7.
go back to reference van Assen S, Agmon-Levin N, Elkayam O, Cervera R, Doran MF, Dougados M, Emery P, Geborek P, Ioannidis JP, Jayne DR, Kallenberg CG, Muller-Ladner U, Shoenfeld Y, Stojanovich L, Valesini G, Wulffraat NM, Bijl M (2011) EULAR recommendations for vaccination in adult patients with autoimmune inflammatory rheumatic diseases. Ann Rheum Dis 70(3):414–422. https://doi.org/10.1136/ard.2010.137216 CrossRefPubMed van Assen S, Agmon-Levin N, Elkayam O, Cervera R, Doran MF, Dougados M, Emery P, Geborek P, Ioannidis JP, Jayne DR, Kallenberg CG, Muller-Ladner U, Shoenfeld Y, Stojanovich L, Valesini G, Wulffraat NM, Bijl M (2011) EULAR recommendations for vaccination in adult patients with autoimmune inflammatory rheumatic diseases. Ann Rheum Dis 70(3):414–422. https://​doi.​org/​10.​1136/​ard.​2010.​137216 CrossRefPubMed
16.
go back to reference Zambon M (1997) Laboratory diagnosis of influenza. In: Nicholson K, Webster R, Hay A (eds) Influenza. Blackwell, Oxford, pp 123–156 Zambon M (1997) Laboratory diagnosis of influenza. In: Nicholson K, Webster R, Hay A (eds) Influenza. Blackwell, Oxford, pp 123–156
26.
go back to reference Meroni PL, Zavaglia D, Girmenia C (2018) Vaccinations in adults with rheumatoid arthritis in an era of new disease-modifying anti-rheumatic drugs. Clin Exp Rheumatol 36(2):317–328PubMed Meroni PL, Zavaglia D, Girmenia C (2018) Vaccinations in adults with rheumatoid arthritis in an era of new disease-modifying anti-rheumatic drugs. Clin Exp Rheumatol 36(2):317–328PubMed
29.
go back to reference Chalmers A, Scheifele D, Patterson C, Williams D, Weber J, Shuckett R, Teufel A (1994) Immunization of patients with rheumatoid arthritis against influenza: a study of vaccine safety and immunogenicity. J Rheumatol 21(7):1203–1206PubMed Chalmers A, Scheifele D, Patterson C, Williams D, Weber J, Shuckett R, Teufel A (1994) Immunization of patients with rheumatoid arthritis against influenza: a study of vaccine safety and immunogenicity. J Rheumatol 21(7):1203–1206PubMed
32.
go back to reference Salemi S, Picchianti-Diamanti A, Germano V, Donatelli I, Di Martino A, Facchini M, Nisini R, Biselli R, Ferlito C, Podesta E, Cappella A, Milanetti F, Rossi F, Amodeo R, Tabacco F, Di Rosa R, Lagana B, DA R (2010) Influenza vaccine administration in rheumatoid arthritis patients under treatment with TNFalpha blockers: safety and immunogenicity. Clin Immunol 134(2):113–120. https://doi.org/10.1016/j.clim.2009.09.014 CrossRefPubMed Salemi S, Picchianti-Diamanti A, Germano V, Donatelli I, Di Martino A, Facchini M, Nisini R, Biselli R, Ferlito C, Podesta E, Cappella A, Milanetti F, Rossi F, Amodeo R, Tabacco F, Di Rosa R, Lagana B, DA R (2010) Influenza vaccine administration in rheumatoid arthritis patients under treatment with TNFalpha blockers: safety and immunogenicity. Clin Immunol 134(2):113–120. https://​doi.​org/​10.​1016/​j.​clim.​2009.​09.​014 CrossRefPubMed
33.
go back to reference Elkayam O, Amir S, Mendelson E, Schwaber M, Grotto I, Wollman J, Arad U, Brill A, Paran D, Levartovsky D, Wigler I, Caspi D, Mandelboim M (2011) Efficacy and safety of vaccination against pandemic 2009 influenza A (H1N1) virus among patients with rheumatic diseases. Arthritis Care Res 63(7):1062–1067. https://doi.org/10.1002/acr.20465 CrossRef Elkayam O, Amir S, Mendelson E, Schwaber M, Grotto I, Wollman J, Arad U, Brill A, Paran D, Levartovsky D, Wigler I, Caspi D, Mandelboim M (2011) Efficacy and safety of vaccination against pandemic 2009 influenza A (H1N1) virus among patients with rheumatic diseases. Arthritis Care Res 63(7):1062–1067. https://​doi.​org/​10.​1002/​acr.​20465 CrossRef
34.
go back to reference Saad CG, Borba EF, Aikawa NE, Silva CA, Pereira RM, Calich AL, Moraes JC, Ribeiro AC, Viana VS, Pasoto SG, Carvalho JF, Franca IL, Guedes LK, Shinjo SK, Sampaio-Barros PD, Caleiro MT, Goncalves CR, Fuller R, Levy-Neto M, Timenetsky Mdo C, Precioso AR, Bonfa E (2011) Immunogenicity and safety of the 2009 non-adjuvanted influenza A/H1N1 vaccine in a large cohort of autoimmune rheumatic diseases. Ann Rheum Dis 70(6):1068–1073. https://doi.org/10.1136/ard.2011.150250 CrossRefPubMed Saad CG, Borba EF, Aikawa NE, Silva CA, Pereira RM, Calich AL, Moraes JC, Ribeiro AC, Viana VS, Pasoto SG, Carvalho JF, Franca IL, Guedes LK, Shinjo SK, Sampaio-Barros PD, Caleiro MT, Goncalves CR, Fuller R, Levy-Neto M, Timenetsky Mdo C, Precioso AR, Bonfa E (2011) Immunogenicity and safety of the 2009 non-adjuvanted influenza A/H1N1 vaccine in a large cohort of autoimmune rheumatic diseases. Ann Rheum Dis 70(6):1068–1073. https://​doi.​org/​10.​1136/​ard.​2011.​150250 CrossRefPubMed
35.
go back to reference Gabay C, Bel M, Combescure C, Ribi C, Meier S, Posfay-Barbe K, Grillet S, Seebach JD, Kaiser L, Wunderli W, Guerne PA, Siegrist CA, Group HNS (2011) Impact of synthetic and biologic disease-modifying antirheumatic drugs on antibody responses to the AS03-adjuvanted pandemic influenza vaccine: a prospective, open-label, parallel-cohort, single-center study. Arthritis Rheum 63(6):1486–1496. https://doi.org/10.1002/art.30325 CrossRefPubMed Gabay C, Bel M, Combescure C, Ribi C, Meier S, Posfay-Barbe K, Grillet S, Seebach JD, Kaiser L, Wunderli W, Guerne PA, Siegrist CA, Group HNS (2011) Impact of synthetic and biologic disease-modifying antirheumatic drugs on antibody responses to the AS03-adjuvanted pandemic influenza vaccine: a prospective, open-label, parallel-cohort, single-center study. Arthritis Rheum 63(6):1486–1496. https://​doi.​org/​10.​1002/​art.​30325 CrossRefPubMed
38.
go back to reference van Assen S, Holvast A, Benne CA, Posthumus MD, van Leeuwen MA, Voskuyl AE, Blom M, Risselada AP, de Haan A, Westra J, Kallenberg CG, Bijl M (2010) Humoral responses after influenza vaccination are severely reduced in patients with rheumatoid arthritis treated with rituximab. Arthritis Rheum 62(1):75–81. https://doi.org/10.1002/art.25033 CrossRefPubMed van Assen S, Holvast A, Benne CA, Posthumus MD, van Leeuwen MA, Voskuyl AE, Blom M, Risselada AP, de Haan A, Westra J, Kallenberg CG, Bijl M (2010) Humoral responses after influenza vaccination are severely reduced in patients with rheumatoid arthritis treated with rituximab. Arthritis Rheum 62(1):75–81. https://​doi.​org/​10.​1002/​art.​25033 CrossRefPubMed
39.
41.
go back to reference Miossi R, Fuller R, Moraes JC, Ribeiro AC, Saad CG, Aikawa NE, Miraglia JL, Ishida MA, Bonfa E, Caleiro MT (2013) Immunogenicity of influenza H1N1 vaccination in mixed connective tissue disease: effect of disease and therapy. Clinics 68(2):129–134CrossRefPubMedPubMedCentral Miossi R, Fuller R, Moraes JC, Ribeiro AC, Saad CG, Aikawa NE, Miraglia JL, Ishida MA, Bonfa E, Caleiro MT (2013) Immunogenicity of influenza H1N1 vaccination in mixed connective tissue disease: effect of disease and therapy. Clinics 68(2):129–134CrossRefPubMedPubMedCentral
44.
go back to reference Okamoto S, Matsuoka S, Takenaka N, Haredy AM, Tanimoto T, Gomi Y, Ishikawa T, Akagi T, Akashi M, Okuno Y, Mori Y, Yamanishi K (2012) Intranasal immunization with a formalin-inactivated human influenza A virus whole-virion vaccine alone and intranasal immunization with a split-virion vaccine with mucosal adjuvants show similar levels of cross-protection. Clin Vaccine Immunol: CVI 19(7):979–990. https://doi.org/10.1128/CVI.00016-12 CrossRefPubMed Okamoto S, Matsuoka S, Takenaka N, Haredy AM, Tanimoto T, Gomi Y, Ishikawa T, Akagi T, Akashi M, Okuno Y, Mori Y, Yamanishi K (2012) Intranasal immunization with a formalin-inactivated human influenza A virus whole-virion vaccine alone and intranasal immunization with a split-virion vaccine with mucosal adjuvants show similar levels of cross-protection. Clin Vaccine Immunol: CVI 19(7):979–990. https://​doi.​org/​10.​1128/​CVI.​00016-12 CrossRefPubMed
45.
go back to reference Nakagawa M, Greenfield W, Moerman-Herzog A, Coleman HN (2015) Cross-reactivity, epitope spreading, and de novo immune stimulation are possible mechanisms of cross-protection of nonvaccine human papillomavirus (HPV) types in recipients of HPV therapeutic vaccines. Clin Vaccine Immunol: CVI 22(7):679–687. https://doi.org/10.1128/CVI.00149-15 CrossRefPubMed Nakagawa M, Greenfield W, Moerman-Herzog A, Coleman HN (2015) Cross-reactivity, epitope spreading, and de novo immune stimulation are possible mechanisms of cross-protection of nonvaccine human papillomavirus (HPV) types in recipients of HPV therapeutic vaccines. Clin Vaccine Immunol: CVI 22(7):679–687. https://​doi.​org/​10.​1128/​CVI.​00149-15 CrossRefPubMed
Metadata
Title
The immunogenicity of seasonal and pandemic influenza vaccination in autoimmune inflammatory rheumatic patients—a 6-month follow-up prospective study
Authors
K. Lakota
K. Perdan-Pirkmajer
S. Sodin-Šemrl
S. Čučnik
V. Šubelj
K. Prosenc
K. Mrak Poljšak
M. Tomšič
A. Ambrožič
S. Praprotnik
Publication date
01-05-2019
Publisher
Springer London
Published in
Clinical Rheumatology / Issue 5/2019
Print ISSN: 0770-3198
Electronic ISSN: 1434-9949
DOI
https://doi.org/10.1007/s10067-019-04439-y

Other articles of this Issue 5/2019

Clinical Rheumatology 5/2019 Go to the issue
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discuss last year's major advances in heart failure and cardiomyopathies.