Heterologous vector versus homologous mRNA COVID-19 booster vaccination in non-seroconverted immunosuppressed patients: a randomized controlled trial

• Published in: Nature communications Vol. 13; no. 1; pp. 5362 - 9
• Main Authors: Mrak, Daniel, Sieghart, Daniela, Simader, Elisabeth, Tobudic, Selma, Radner, Helga, Mandl, Peter, Göschl, Lisa, Koblischke, Maximilian, Hommer, Nikolaus, Wagner, Angelika, Mayer, Margareta, Schubert, Lorenz, Hartl, Lukas, Kozbial, Karin, Hofer, Philipp, Kartnig, Felix, Hummel, Thomas, Kerschbaumer, Andreas, Deimel, Thomas, Puchner, Antonia, Gudipati, Venugopal, Thalhammer, Renate, Munda, Petra, Uyanik-Ünal, Keziban, Zuckermann, Andreas, Novacek, Gottfried, Reiberger, Thomas, Garner-Spitzer, Erika, Reindl-Schwaighofer, Roman, Kain, Renate, Winkler, Stefan, Smolen, Josef S., Stiasny, Karin, Fischer, Gottfried F., Perkmann, Thomas, Haslacher, Helmuth, Zeitlinger, Markus, Wiedermann, Ursula, Aberle, Judith H., Aletaha, Daniel, Heinz, Leonhard X., Bonelli, Michael
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 12.09.2022; Nature Publishing Group; Nature Portfolio
• Subjects: 13/31; 631/250/590/2293; 631/326/596/4130; 692/308/2779/109; 692/699/249; 82/1; Antibodies; Antibodies, Viral; BNT162 Vaccine; ChAdOx1 nCoV-19; Clinical trials; Coronaviruses; COVID-19; COVID-19 - prevention & control; COVID-19 vaccines; COVID-19 Vaccines - adverse effects; Dosage; Firing rate; Homology; Humanities and Social Sciences; Humans; Immune response; Immune response (cell-mediated); Immunization; Immunization, Secondary; Lymphocytes T; mRNA; mRNA Vaccines; multidisciplinary; Patients; Regression analysis; RNA, Messenger; SARS-CoV-2 - genetics; Science; Science (multidisciplinary); Seroconversion; Severe acute respiratory syndrome; Severe acute respiratory syndrome coronavirus 2; Vaccination; Vaccines; Vaccines, Synthetic
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-022-33036-y

Impaired response to COVID-19 vaccination is of particular concern in immunosuppressed patients. To determine the best vaccination strategy for this vulnerable group we performed a single center, 1:1 randomized blinded clinical trial. Patients who failed to seroconvert upon two mRNA vaccinations (BNT162b2 or mRNA-1273) are randomized to receive either a third dose of the same mRNA or the vector vaccine ChAdOx1 nCoV-19. Primary endpoint is the difference in SARS-CoV-2 spike antibody seroconversion rate between vector and mRNA vaccinated patients four weeks after the third dose. Secondary outcomes include cellular immune responses. Seroconversion rates at week four are significantly higher in the mRNA (homologous vaccination, 15/24, 63%) as compared to the vector vaccine group (heterologous vaccination, 4/22, 18%). SARS-CoV-2-specific T-cell responses are reduced but could be increased after a third dose of either vector or mRNA vaccine. In a multivariable logistic regression analysis, patient age and vaccine type are associated with seroconversion. No serious adverse event is attributed to COVID-19 booster vaccination. Efficacy and safety data underline the importance of a booster vaccination and support the use of a homologous mRNA booster vaccination in immunosuppressed patients. Trial registration: EudraCT No.: 2021-002693-10. Optimizing COVID-19 vaccination strategies for patients under immunosuppressive medication is of high importance. In this clinical trial including non-seroconverted immunosuppressed patients, a homologous mRNA booster vaccination resulted in higher seroconversion rate than a switch to a vector-based vaccine.