Abstract :
[en] [en] PURPOSE: Patients with cancer display reduced humoral responses after double-dose COVID-19 vaccination, whereas their cellular response is more comparable with that in healthy individuals. Recent studies demonstrated that a third vaccination dose boosts these immune responses, both in healthy people and patients with cancer. Because of the availability of many different COVID-19 vaccines, many people have been boosted with a different vaccine from the one used for double-dose vaccination. Data on such alternative vaccination schedules are scarce. This prospective study compares a third dose of BNT162b2 after double-dose BNT162b2 (homologous) versus ChAdOx1 (heterologous) vaccination in patients with cancer.
EXPERIMENTAL DESIGN: A total of 442 subjects (315 patients and 127 healthy) received a third dose of BNT162b2 (230 homologous vs. 212 heterologous). Vaccine-induced adverse events (AE) were captured up to 7 days after vaccination. Humoral immunity was assessed by SARS-CoV-2 anti-S1 IgG antibody levels and SARS-CoV-2 50% neutralization titers (NT50) against Wuhan and BA.1 Omicron strains. Cellular immunity was examined by analyzing CD4+ and CD8+ T-cell responses against SARS-CoV-2-specific S1 and S2 peptides.
RESULTS: Local AEs were more common after heterologous boosting. SARS-CoV-2 anti-S1 IgG antibody levels did not differ significantly between homologous and heterologous boosted subjects [GMT 1,755.90 BAU/mL (95% CI, 1,276.95-2,414.48) vs. 1,495.82 BAU/mL (95% CI, 1,131.48-1,977.46)]. However, homologous-boosted subjects show significantly higher NT50 values against BA.1 Omicron. Subjects receiving heterologous boosting demonstrated increased spike-specific CD8+ T cells, including higher IFNγ and TNFα levels.
CONCLUSIONS: In patients with cancer who received double-dose ChAdOx1, a third heterologous dose of BNT162b2 was able to close the gap in antibody response.
Funding text :
We kindly thank the B-VOICE and Tri-VOICE plus patients and HEAL-V participants for participation; the nursing staff members at the Day Care Unit of the Antwerp University Hospital and AZ Maria Middelares; and the staff members of the Biobank Antwerp and all recruiting physicians: Sevilay Altintas, Zwi Berneman, Sarah Debussche, Charlotte De Bondt, Ximena Elzo-Kraemer, Veerle Galle, Felix Gremonprez, Konstantinos Papadimitriou, Jo Raskin, Marika Rasschaert, Kirsten Saevels, Wiebren Tjalma, Xuan Bich Trinh, Christophe Van Berckelaer, Jan Van den Brande, Ann Van de Velde and Anke Verlinden. We are grateful to Leo Heyndrickx, Johan Michiels, and Betty Willems for neutralising antibody testing, to Hans De Reu, Stefanie Peeters, Carole Faghel, Celine Merlin, and Ho Wa Lau for T-cell analysis, and to the clinical biology study team for performing serologic analysis. We are thankful to Silke Raats, Isolde Van der Massen, Sanne Wouters, and Sven De Keersmaecker for logistic support and coordination and to Abraham Lin for proofreading of the manuscript. In addition, we thank the B-VOICE, Tri-VOICE plus, and HEAL-V study teams for patient inclusion and sample collection. This work was supported by the Belgian Government through Sciensano (grant nos. COVID-19_SC004, COVID-19_SC059, COVID-19_SC061), Kom op tegen Kanker (KOTK_UZA/ 2020/12604/1), Methusalem (FFB150082, FFB200035), and UA core facility funding (KF120000). T. Vandamme is holder of Senior Clinical Investigator grant 1803723N of the Research Foundation - Flanders (Belgium) (FWO).
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