Purpose: Cancer patients display reduced humoral responses after double-dose COVID-19 vaccination while their cellular response is more comparable to that in healthy individuals. Recent studies demonstrated that a third vaccination dose boosts these immune responses, both in healthy people and cancer patients. Due to 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 cancer patients. Experimental design: 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 SARSCoV-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 1755.90 BAU/mL [95% CI 1276.95-2414.48] vs 1495.82 BAU/mL (95% CI 1131.48-1977.46)). 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 cancer patients who received double-dose ChAdOx1, a third heterologous dose of BNT162b2 was able to close the gap in antibody response.

<div>Purpose:<p>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.</p>Experimental Design:<p>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.</p>Results:<p>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.</p>Conclusions:<p>In patients with cancer who received double-dose ChAdOx1, a third heterologous dose of BNT162b2 was able to close the gap in antibody response.</p></div>

<div>Purpose:<p>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.</p>Experimental Design:<p>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.</p>Results:<p>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.</p>Conclusions:<p>In patients with cancer who received double-dose ChAdOx1, a third heterologous dose of BNT162b2 was able to close the gap in antibody response.</p></div>

<p>Supplementary Figure 1: Correlation betweenSARS-CoV-2 anti-S1 IgG antibody titers and NT50 values against Wuhan and BA.1 Omicron strains post homologous or heterologous booster vaccination in cancer patients and healthy individuals.</p>