Limited T cell response to SARS-CoV-2 mRNA vaccine among patients with cancer receiving different cancer treatments.

Introduction: Patients with cancer (PC) are at high risk of acquiring COVID-19 and can develop more serious complications. Deeper understanding of vaccines immunogenicity in this population is crucial for adequately planning vaccines programs. The ONCOVac study aimed to comprehensively assess the immunogenicity of mRNA-1273 vaccine in terms of humoral and cellular response.
Methods: We conducted a prospective, single-center study including patients with solid tumours treated with cyclin-dependent kinases 4 and 6 inhibitors (CDK4/6i), immunotherapy (IT) or chemotherapy (CT). Patients were enrolled previously to vaccination with mRNA-1273. We also involved health care workers (HCW) to serve as a control group. We took blood samples before first dose administration (BL), after first dose (1D), and after second dose (2D). The primary objective was to compare the rate and magnitude of T cell response after second dose whereas safety and humoral response were defined as secondary objectives. We also collected patient reported outcomes after both the first and second vaccine dose and a six-month follow-up period to diagnose incident COVID-19 cases was planned.
Results: The rate of specific anti-S serologic positivity (anti-S IgG cut-off point at 7,14 BAU/mL) was significantly higher in HCW compared to PC after 1D (100% versus 83.8%; p = 0.04), but similar after 2D (100% versus 95.8%; p = 0.5). This difference after 1D was driven by PC treated with CT (100% versus 64.5%; p = 0.001). Cellular response after 2D was significantly lower in PC than in HCW for both CD4+ (91.7% versus 59.7%; p = 0.001) and CD8+ (94.4% versus 55.6%; p < 0.001) T cells. We found a difference on pre-existing CD4+ T cell response in HCW comparing to PC (36% and 17%, p = 0.03); without difference in pre-existing CD8+ T cell response (31% and 23%, p = 0.5). After excluding patients with pre-existing T cell response, PC achieved even lower CD4+ (50.9% versus 95.5%, p < 0.001) and CD8+ (45.5% versus 95.5%, p < 0.001) T cell response compared with HCW. Regarding safety, PC reported notably more adverse events than HCW (96.6% versus 69.2%, p < 0.001).
Conclusion: We demonstrated that PC showed a similar humoral response but a lower T cell response following two doses of mRNA-1273 vaccination. Further studies are needed to complement our results and determine the implication of low T cell response on clinical protection of PC against COVID-19.
Competing Interests: Conflict of interest statement The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Alfonso Cortes declares the payment for presentations/speaker bureaus/manuscript-writing/educational events from GSK, AstraZeneca, Roche, MSD and Eisai. Alfonso Cortes declares consulting fees from Clovis, Lilly, Pfizer, GSK, Ferrer and Roche. Alfonso Cortes has received research grants from Pfizer. Alfonso Cortes declares support for attending meetings from Roche, Daiichi and Pfzer. Alfonso Cortes is co-founder of ONCARE. Jose Luis Casado and Federico Longo have not conflict of interest to declare. Juan José Serrano declares speaker bureau from Pierre-Fabre and travel/accomodation/expenses from Novartis. Cristina Saavedra declares travel/accomodation/expenses from Lilly and Pfizer. Hector Velasco, Alejandro Vallejo and Adrian San Miguel have not conflict of interest to declare. Jesus Chamorro and Diana Rosero have not conflict of interest to declare. María Fernandez, María Gion and Noelia Martinez have not conflict of interest to declare. Ainara Soria has not conflict of interest to declare. Teresa Alonso declares: Scientific Consultancy Role (speaker and advisory role) and travel grant from IPSEN, Pfizer, Bayer, Sanofi, Janssen, Astellas, Adacap, Eisai, Lilly, Novartis, BMS, Roche. Teresa Alonso declares the participation in Clinical trials from Roche, BMS, MSD, Pfizer, Novartis, IPSEN, Exelixis, Astrazeneca-Medimmune, Janssen, Lilly, Eisai, Astellas. Teresa Alonso declares research support from Roche, Pfizer, IPSEN. Iñigo Martinez and Yolanda Lage have not conflict of interest to declare. Elena López declares to receive advisory/consultancy honorarium from AstraZeneca, Pfizer, Roche, Novartis. Elena López has received speaker bureau/expert testimony honorarium from Roche, Novartis , Eisai, Astra Zeneca; and has received travel/accommodation/expenses from Roche, Novartis. María Eugenia Olmedo has not conflict of interest to declare. Pablo Reguera has not conflict of interest to declare. Pablo Gajate declares travel and educational support from BMS, MSD, Pfizer, Ipsen, Sanofi-Genzyne, Roche and Jansen. Pablo Gajate declares advisor and delivered lectures for BMS, MSD, Merck Serono, Pfizer, Ipsen, Roche, Adacap, Eisai, Sanofi-Genzyme, Novartis and Jansen. Javier Molina declares consultant, advisory or speaker roles for IPSEN, Roche, Pfizer, Sanofi, Janssen, and BMS. Javier Molina has received research grants from Pfizer, IPSEN and Roche. Eva Guerra declares: advisory/consultancy honorarium from AstraZeneca-MSD, Clovis Oncology, GSK-Tesaro, PharmaMar, Roche. Eva Guerra has received speaker bureau/expert testimony honorarium from AstraZeneca, PharmaMar, Roche, GSK; and has received travel/accommodation/expenses from Roche, TESARO, and Baxter. Raquel Fuentes, Beatriz Romero and Mario J Rodriguez-Dominguez have not conflict of interest. Alfredo Carrato has not conflict of interest to declare.
(Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)