Humoral and Cellular Immune Responses against SARS-CoV-2 after Third Dose BNT162b2 following Double-Dose Vaccination with BNT162b2 versus ChAdOx1 in Patients with Cancer

Abstract

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.

Humoral Response after SARS-CoV-2 Vaccination in Prostate Cancer Patients

“…Many studies by other authors showed that cancer patients had a reduced humoral response after receiving a double dose of the COVID-19 vaccine compared to healthy individuals [37][38][39][40][41].…”

Low booster uptake in cancer patients despite health benefits

“…Serial boosters may continue to strengthen and help maintain the humoral immune response in the vast majority of patients with cancer under active treatment. Still some patients, including those receiving anti-CD20 therapy, CD19-directed chimeric antigen receptor T-cell therapy and ibrutinib, [11] , [19,28] may require alternative protective measures such as recombinant antibodies or high titer intravenous immunoglobulin.…”

“…[5] Several studies of the Omicron (B.1.1.529) subvariants reported heightened capacity for immune evasion, [6] and reduced vaccine effectiveness for first-generation monovalent COVID-19 vaccines. [7] Other reports suggest that additional doses of the monovalent mRNA vaccines, [8,9] heterologous boosting, [10,11] and the bivalent mRNA vaccines provide additional immune protection to SARS-CoV-2 B.1.1.529 infection and severe COVID-19 illness. [12] For patients with cancer, evidence suggests that primer vaccinations elicit lower antibody titers compared to healthy individuals, albeit dependent on disease state, co-morbidities, and anticancer treatment status.…”

“…[12] For patients with cancer, evidence suggests that primer vaccinations elicit lower antibody titers compared to healthy individuals, albeit dependent on disease state, co-morbidities, and anticancer treatment status. [13][14][15][16][17][18] Subsequent booster vaccinations have been reported to restore and increase antibody titers in patients similar to healthy controls, [11,18,19] except for patients receiving B-cell-depleting therapies and chemotherapies. [11,19] However, even seronegative individuals appear capable of mounting T-cell responses, [14,20] and some data suggest that T-cell responses are more robust over time compared to antibody levels.…”

“…[13][14][15][16][17][18] Subsequent booster vaccinations have been reported to restore and increase antibody titers in patients similar to healthy controls, [11,18,19] except for patients receiving B-cell-depleting therapies and chemotherapies. [11,19] However, even seronegative individuals appear capable of mounting T-cell responses, [14,20] and some data suggest that T-cell responses are more robust over time compared to antibody levels. [21] Changes in vaccine availability and the evolving nature of the science and public health recommendations for additional doses have likely impacted the psychosocial wellbeing of patients.…”