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VACCIM

​VACCIM – Investigation of immune responses to SARS-CoV-2 vaccination and infection.​​


​This study aims to examine the immediate and long-term immune responses to COVID-19 vaccination and infection in populations at increased risk of COVID-19 infection. Participants in the study include people living with HIV, haematological cancer or lung illnesses, solid organ transplant recipients, and patients with psoriasis or neurological diseases receiving biological treatments or methotrexate, as well as a large group of health care workers from Copenhagen University Hospitals. The study investigates neutralising antibodies and cellular responses to SARS-CoV-2 vaccination or infection. ​​​

​This study is no longer including patients. Data analysis is currently ongoing and published results for sub-populations of the study are summarized below:

 

After solid organ transplantation

We found decreased humoral response rates in solid organ transplant recipients compared to healthy individuals up to six months after the second dose of the COVID-19 vaccine, BNT162b2. The decline was most pronounced in individuals who received a lung or kidney compared to liver transplant recipients. A similar pattern was seen one year after administration of the first dose after receiving a third vaccine dose. However, in solid organ transplant recipients with a previous infection humoral and cellular immune responses were comparable to the controls.

HIV

In people with HIV, we found that two doses of the COVID-19 vaccine, BNT162b2, induced a strong antibody response although slightly weaker than in the control group of healthcare workers. CD4 counts and HIV viremia did not affect the antibody response in this cohort.

Psoriasis

Patients with psoriasis had persistence of both humoral and cellular responses 6 months after their first COVD-19 vaccination although they had a faster decline in their antibody response than controls. Patients with psoriasis treated with anti-TNF agents showed faster waning of immunity while our findings did not indicate impairment of immunity in patients receiving methotrexate.

Lung illnesses

Patients with chronic pulmonary diseases established functional humoral responses to vaccination, however lower than controls. Increasing age, having more underlying comorbidities and using oral steroids or other immunosuppressive drugs were associated with poorer immunological responses.

Healthcare workers

In the group of healthcare workers, we found that lower age and female sex was associated with higher antibody response to the first dose of an mRNA based COVID-19 vaccine. Previous SARS-CoV-2 infection was associated with a more rapid and robust response to the vaccine than individuals who had not been infected. Six months after receiving the second vaccine dose, humoral responses decreased in all age groups.

In a sub-study of saliva samples, SARS-CoV-2-specific antibodies were elevated in previously infected individuals compared to infection-naive individuals, however the antibody concentrations waned quickly after vaccination, suggesting a rapid decline in antibody-mediated saliva immunity against SARS-CoV-2.​

​Department of Infectious Diseases, Rigshospitalet

  • Susanne Dam Poulsen, Professor, MD, Senior Consultant
  • Line Dam Heftdal, MD, PhD Student
  • Sebastian Rask Hamm, MD, PhD Student
  • Dina Leth Møller, MD, PhD Student

Department of Clinical Immunology, Section 7631, Laboratory of Molecular Medicine, Rigshospitalet

  • Peter Garred, Professor, Senior Consultant
  • Cecilie Bo Hansen, MD, PhD Student
  • Laura Pérez-Alós, PhD Student

Department of Clinical Immunology, Section 2034, Rigshospitalet

  • Sisse Rye Ostrowski, Professor, Senior Consultant
  • Erik Sørensen, Laboratory Leader

Department of Clinical Biochemistry (KBA), Rigshospitalet

  • Ruth Frikke-Schmidt, Professor, Senior Consultant
  • Linda Maria Hilsted, Chief Physician

Department of Cardiology, Rigshospitalet

  • Henning Bundgaard, Professor, Senior Consultant
  • Michael Perch, Chief Physician

Department of Haematology, Rigshospitalet

  • Kirsten Grønbæk, Professor, Senior Consultant

Department of Surgical Gastroenterology, Rigshospitalet

  • Allan Rasmussen, Senior Consultant

Department of Nephrology, Rigshospitalet

  • Søren Schwartz Sørensen, Professor, Senior Consultant

Department of Neurology, Rigshospitalet

  • John Vissing, Professor, Senior Consultant
  • Finn Sellebjerg, Professor, Senior Consultant

Department of Emergency Medicine, Herlev-Gentofte Hospital

  • Kasper Iversen, Professor, Senior Consultant

Department of Cardiology, Herlev-Gentofte Hospital

  • Kasper Iversen, Professor, Senior Consultant
  • Kamille Fogh, MD, PhD Student
  • Rasmus Bo Hasselbalch, MD, PhD

Department of Dermatology and Allergy, Gentofte Hospital

  • Lone Skov, Professor, Senior Consultant
  • Amanda Kvist-Hansen, MD, PhD

Department of Respiratory Medicine, Gentofte Hospital

  • Jens-Ulrik Stæhr Jensen, Professor, Senior Consultant

Department of Respiratory Medicine and Infectious Diseases, Nordsjællands Hospital

  • Zitta Barrella Harboe, MD, PhD


Funding​

  • Bio- and Genome bank Denmark
  • Læge Sofus Carl Emil Friis og Hustru Olga Doris Friis Legat
  • Rigshospitalet Research Council​​


​Ongoing PhD-projects

  • ​“Immune Responses to COVID-19 Vaccines in Immunocompromised Patients– Line Dam Heftdal, Læge, PhD-studerende​

Publicat​​ions

Münter R, Sørensen E, Hasselbalch RB, Christensen E, Nielsen SD, Garred P, Ostrowski SR, Bundgaard H, Iversen KK, Andresen TL, Larsen JB. Investigating Generation of Antibodies against the Lipid Nanoparticle Vector Following COVID-19 Vaccination with an mRNA Vaccine. Mol Pharm. 2023 Mar 23. doi:

10.1021/acs.molpharmaceut.2c01036. Epub ahead of print.​

Madsen JR, Holm BE, Pérez-Alós L, Bayarri-Olmos R, Rosbjerg A, Fogh K, Pries-Heje MM, Møller DL, Hansen CB, Heftdal LD, Hasselbalch RB, Hamm SR, Frikke-Schmidt R, Hilsted L, Nielsen SD, Iversen KK, Bundgaard H, Garred P. Short-Lived Antibody-Mediated Saliva Immunity against SARS-CoV-2 after Vaccination. Microbiol Spectr. 2023 Mar 6:e0494722. doi: 10.1128/spectrum.04947-22. Epub ahead of print.

Rezahosseini O, Hamm SR, Heftdal LD, Pérez-Alós L, Møller DL, Perch M, Madsen JR, Hald A, Hansen CB, Armenteros JJA, Pries-Heje MM, Hasselbalch RB, Fogh K, Frikke-Schmidt R, Hilsted LM, Sørensen E, Ostrowski SR, Harboe ZB, Iversen K, Bundgaard H, Sørensen SS, Rasmussen A, Garred P, Nielsen SD. Humoral and T-cell response 12 months after the first BNT162b2 vaccination in solid organ transplant recipients and controls: Kinetics, associated factors, and role of SARS-CoV-2 infection. Front Immunol. 2023 Jan 13;13:1075423. doi: 10.3389/fimmu.2022.1075423.

Kvist-Hansen A, Pérez-Alós L, Al-Sofi RF, Heftdal LD, Hamm SR, Møller DL, Pries-Heje MM, Fogh K, Hansen CB, Hasselbalch RB, Madsen JR, Armenteros JJA, Frikke-Schmidt R, Hilsted L, Sørensen E, Ostrowski SR, Bundgaard H, Nielsen SD, Iversen K, Zachariae C, Garred P, Skov L. Waning humoral and cellular immunity after COVID-19 vaccination in patients with psoriasis treated with methotrexate and biologics: a cohort study. Br J Dermatol. 2023 Jan 27:ljad023. doi: 10.1093/bjd/ljad023. Epub ahead of print.

Harboe ZB, Hamm SR, Pérez-Alós L, Sivapalan P, Priemé H, Wilcke T, Kjeldgaard P, Shaker S, Svorre Jordan A, Møller DL, Heftdal LD, Madsen JR, Bayarri-Olmos R, Hansen CB, Pries-Heje MM, Hasselbalch RB, Fogh K, Armenteros JJA, Hilsted L, Sørensen E, Lindegaard B, Browatzki A, Biering-Sørensen T, Frikke-Schmidt R, Ostrowski SR, Iversen KK, Bundgaard H, Nielsen SD, Garred P, Jensen JS. Antibody responses and risk factors associated with impaired immunological outcomes following two doses of BNT162b2 COVID-19 vaccination in patients with chronic pulmonary diseases. BMJ Open Respir Res. 2022 Jul;9(1):e001268. doi: 10.1136/bmjresp-2022-001268.

Heftdal LD, Knudsen AD, Hamm SR, Hansen CB, Møller DL, Pries-Heje M, Fogh K, Hasselbalch RB, Jarlhelt I, Pérez-Alós L, Hilsted LM, Ostrowski SR, Gerstoft J, Grønbaek K, Bundgaard H, Iversen K, Garred P, Nielsen SD. Humoral response to two doses of BNT162b2 vaccination in people with HIV. J Intern Med. 2022 Apr;291(4):513-518. doi: 10.1111/joim.13419. Epub 2021 Dec 16.

Pérez-Alós L, Armenteros JJA, Madsen JR, Hansen CB, Jarlhelt I, Hamm SR, Heftdal LD, Pries-Heje MM, Møller DL, Fogh K, Hasselbalch RB, Rosbjerg A, Brunak S, Sørensen E, Larsen MAH, Ostrowski SR, Frikke-Schmidt R, Bayarri-Olmos R, Hilsted LM, Iversen KK, Bundgaard H, Nielsen SD, Garred P. Modeling of waning immunity after SARS-CoV-2 vaccination and influencing factors. Nat Commun. 2022 Mar 28;13(1):1614. doi: 10.1038/s41467-022-29225-4.

Hamm SR, Møller DL, Pérez-Alós L, Hansen CB, Pries-Heje MM, Heftdal LD, Hasselbalch RB, Fogh K, Madsen JR, Almagro Armenteros JJ, Knudsen AD, Poulsen JR, Frikke-Schmidt R, Hilsted LM, Sørensen E, Ostrowski SR, Harboe ZB, Perch M, Sørensen SS, Rasmussen A, Bundgaard H, Garred P, Iversen K, Nielsen SD. Decline in Antibody Concentration 6 Months After Two Doses of SARS-CoV-2 BNT162b2 Vaccine in Solid Organ Transplant Recipients and Healthy Controls. Front Immunol. 2022 Feb 23;13:832501. doi: 10.3389/fimmu.2022.832501.

Hansen CB, Jarlhelt I, Hasselbalch RB, Hamm SR, Fogh K, Pries-Heje MM, Møller DL, Heftdal LD, Pérez-Alós L, Sørensen E, Larsen MAH, Skjoedt MO, Ostrowski SR, Frikke-Schmidt R, Bayarri-Olmos R, Hilsted LM, Bundgaard H, Nielsen SD, Iversen KK, Garred P. Antibody-dependent neutralizing capacity of the SARS-CoV-2 vaccine BNT162b2 with and without previous COVID-19 priming. J Intern Med. 2021 Dec;290(6):1272-1274. doi: 10.1111/joim.13366. Epub 2021 Aug 2.

Bayarri-Olmos R, Jarlhelt I, Johnsen LB, Hansen CB, Helgstrand C, Rose Bjelke J, Matthiesen F, Nielsen SD, Iversen KK, Ostrowski SR, Bundgaard H, Frikke-Schmidt R, Garred P, Skjoedt MO. Functional Effects of Receptor-Binding Domain Mutations of SARS-CoV-2 B.1.351 and P.1 Variants. Front Immunol. 2021 Oct 7;12:757197. doi: 10.3389/fimmu.2021.757197.

Presentations at Scientific meetings

  • CROI Conference: February 2022, Online, USA, virtual poster presentation

  • EACS Conference: October 2021, London, UK, ePoster

  • EHA Congress: June 2022, Wien, Austria, oral presentation

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