Repeated SARS-CoV-2 vaccination in cancer patients treated with immune checkpoint inhibitors: induction of high-avidity anti-RBD neutralizing antibodies.


Journal

International journal of clinical oncology
ISSN: 1437-7772
Titre abrégé: Int J Clin Oncol
Pays: Japan
ID NLM: 9616295

Informations de publication

Date de publication:
Mar 2023
Historique:
received: 09 08 2022
accepted: 04 01 2023
pubmed: 24 1 2023
medline: 9 3 2023
entrez: 23 1 2023
Statut: ppublish

Résumé

Cancer patients are more vulnerable to COVID-19 and are thus given high priority in vaccination campaigns. In solid cancer patients treated with checkpoint inhibitors, we evaluated the amount of anti-RBD and neutralizing antibodies and antibody avidity after two or three doses of the vaccine. Thirty-eight solid cancer patients, 15 untreated hematological patients and 21 healthy subjects were enrolled in the study. Blood was collected before the first dose (T0), 21 days after the second (T2) and in 18 solid cancer patients also 15 days after the third dose of vaccine (T3). IgG, IgM and IgA anti-RBD antibodies were detected by ELISA. Neutralizing antibodies were measured testing the inhibition of RBD binding to ACE2. Antibody avidity was evaluated in 18 patients by a urea avidity ELISA. IgG anti-RBD antibodies were produced in 65.8% of the cancer patients at T2, and in 60% of hematological patients at levels lower than healthy controls. IgM and IgA anti-RBD antibodies were also produced in 5.3% and 21% cancer patients, respectively. At T3, a significant increase in anti-RBD IgG levels was observed. Neutralizing antibodies were produced in 68.4% of cancer patients as compared with 93% of untreated hematological patients and 100% of controls, at titers lower than in healthy subjects. At T3, neutralizing antibodies and avidity of IgG anti-RBD increased; 6/18 patients negative at T2 developed neutralizing antibodies at T3. The data indicate that in cancer patients mRNA vaccine induces high avidity anti-RBD antibodies and neutralizing antibodies that increase after the third dose. The process of induction and selection of high-affinity antibodies is apparently unaffected by the treatment with anti-PD-1 or anti-PD-L1 antibodies.

Sections du résumé

BACKGROUND BACKGROUND
Cancer patients are more vulnerable to COVID-19 and are thus given high priority in vaccination campaigns. In solid cancer patients treated with checkpoint inhibitors, we evaluated the amount of anti-RBD and neutralizing antibodies and antibody avidity after two or three doses of the vaccine.
METHODS METHODS
Thirty-eight solid cancer patients, 15 untreated hematological patients and 21 healthy subjects were enrolled in the study. Blood was collected before the first dose (T0), 21 days after the second (T2) and in 18 solid cancer patients also 15 days after the third dose of vaccine (T3). IgG, IgM and IgA anti-RBD antibodies were detected by ELISA. Neutralizing antibodies were measured testing the inhibition of RBD binding to ACE2. Antibody avidity was evaluated in 18 patients by a urea avidity ELISA.
RESULTS RESULTS
IgG anti-RBD antibodies were produced in 65.8% of the cancer patients at T2, and in 60% of hematological patients at levels lower than healthy controls. IgM and IgA anti-RBD antibodies were also produced in 5.3% and 21% cancer patients, respectively. At T3, a significant increase in anti-RBD IgG levels was observed. Neutralizing antibodies were produced in 68.4% of cancer patients as compared with 93% of untreated hematological patients and 100% of controls, at titers lower than in healthy subjects. At T3, neutralizing antibodies and avidity of IgG anti-RBD increased; 6/18 patients negative at T2 developed neutralizing antibodies at T3.
CONCLUSION CONCLUSIONS
The data indicate that in cancer patients mRNA vaccine induces high avidity anti-RBD antibodies and neutralizing antibodies that increase after the third dose. The process of induction and selection of high-affinity antibodies is apparently unaffected by the treatment with anti-PD-1 or anti-PD-L1 antibodies.

Identifiants

pubmed: 36689013
doi: 10.1007/s10147-023-02295-0
pii: 10.1007/s10147-023-02295-0
pmc: PMC9869844
doi:

Substances chimiques

Immune Checkpoint Inhibitors 0
COVID-19 Vaccines 0
Antibodies, Neutralizing 0
Immunoglobulin A 0
Immunoglobulin G 0
Immunoglobulin M 0
Antibodies, Viral 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

363-369

Subventions

Organisme : Ministero della Salute
ID : COVID-2020-12371849

Commentaires et corrections

Type : ErratumIn

Informations de copyright

© 2023. The Author(s).

Références

Lee LY, Cazier JB, Angelis V et al (2020) COVID-19 mortality in patients with cancer on chemotherapy or other anticancer treatments: a prospective cohort study. Lancet 395(10241):1919–1926. https://doi.org/10.1016/S0140-6736(20)31173-9
doi: 10.1016/S0140-6736(20)31173-9 pubmed: 32473682 pmcid: 7255715
Agbarya A, Sarel I, Ziv-Baran T et al (2021) Efficacy of the mRNA-based BNT162b2 COVID-19 vaccine in patients with solid malignancies treated with anti-neoplastic drugs. Cancers (Basel) 13(16):4191. https://doi.org/10.3390/cancers13164191
doi: 10.3390/cancers13164191 pubmed: 34439346
Ligumsky H, Safadi E, Etan T et al (2021) Immunogenicity and safety of the BNT162b2 mRNA COVID-19 vaccine among actively treated cancer patients. J Natl Cancer Inst 1:1–52. https://doi.org/10.1093/jnci/djab174
doi: 10.1093/jnci/djab174
Cavanna L, Citterio C, Biasini C et al (2021) COVID-19 vaccines in adult cancer patients with solid tumours undergoing active treatment: seropositivity and safety. A prospective observational study in Italy. Eur J Cancer 157:441–449. https://doi.org/10.1016/j.ejca.2021.08.035
doi: 10.1016/j.ejca.2021.08.035 pubmed: 34601285 pmcid: 8410513
Grinshpun A, Rottenberg Y, Ben-Dov IZ et al (2021) Serologic response to COVID-19 infection and/or vaccine in cancer patients on active treatment. ESMO Open 6(6):100283. https://doi.org/10.1016/j.esmoop.2021.100283
doi: 10.1016/j.esmoop.2021.100283 pubmed: 34634634 pmcid: 8469519
Goshen-Lago T, Waldhorn I, Holland R et al (2021) Serologic status and toxic effects of the SARS-CoV-2 BNT162b2 vaccine in patients undergoing treatment for cancer. JAMA Oncol 7(10):1507–1513. https://doi.org/10.1001/jamaoncol.2021.2675
doi: 10.1001/jamaoncol.2021.2675 pubmed: 34236381
Thakkar A, Pradhan K, Jindal S et al (2021) Patterns of seroconversion for SARS-CoV2-IgG in patients with malignant disease and association with anticancer therapy. Nat Cancer 2(4):392–399. https://doi.org/10.1038/s43018-021-00191-y
doi: 10.1038/s43018-021-00191-y pubmed: 34661163 pmcid: 8519533
Becerril-Gaitan A, Vaca-Cartagena BF, Ferrigno AS et al (2021) Immunogenicity and risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection after coronavirus disease 2019 (COVID-19) vaccination in patients with cancer: a systematic review and meta-analysis. Eur J Cancer 160:243–260. https://doi.org/10.1016/j.ejca.2021.10.014
doi: 10.1016/j.ejca.2021.10.014 pubmed: 34794855 pmcid: 8548030
Peeters M, Verbruggen L, Teuwen L et al (2021) Reduced humoral immune response after BNT162b2 coronavirus disease 2019 messenger RNA vaccination in cancer patients under antineoplastic treatment. ESMO Open 6(5):100274. https://doi.org/10.1016/j.esmoop.2021.100274
doi: 10.1016/j.esmoop.2021.100274 pubmed: 34597941 pmcid: 8423808
Fendler A, Shepherd STC, Au L et al (2021) Adaptive immunity and neutralizing antibodies against SARS-CoV-2 variants of concern following vaccination in patients with cancer: the CAPTURE study. Nat Cancer 2:1321–1337. https://doi.org/10.1038/s43018-021-00274-w
doi: 10.1038/s43018-021-00274-w pubmed: 35121900 pmcid: 7612125
Zeng C, Evans JP, Reisinger S et al (2021) Impaired neutralizing antibody response to COVID-19 mRNA vaccines in cancer patients. Cell Biosci 11(1):197. https://doi.org/10.1186/s13578-021-00713-2
doi: 10.1186/s13578-021-00713-2 pubmed: 34802457 pmcid: 8606166
Terpos E, Zagouri F, Liontos M et al (2021) Low titers of SARS-CoV-2 neutralizing antibodies after first vaccination dose in cancer patients receiving checkpoint inhibitors. J Hematol Oncol 14(1):86. https://doi.org/10.1186/s13045-021-01099-x
doi: 10.1186/s13045-021-01099-x pubmed: 34059088 pmcid: 8165511
Rottenberg Y, Grinshpun A, Ben-Dov IZ et al (2021) Assessment of response to a third dose of the SARS-CoV-2 BNT162b2 mRNA vaccine in patients with solid tumors undergoing active treatment. JAMA Oncol. https://doi.org/10.1001/jamaoncol.2021.6764
doi: 10.1001/jamaoncol.2021.6764 pmcid: 8611511
Akkaya M, Kwak K, Pierce SK (2020) B cell memory: building two walls of protection against pathogens. Nat Rev Immunol 20(4):229–238. https://doi.org/10.1038/s41577-019-0244-2
doi: 10.1038/s41577-019-0244-2 pubmed: 31836872
Pratesi F, Caruso T, Testa D et al (2021) BNT162b2 mRNA SARS-CoV-2 vaccine elicits high avidity and neutralizing antibodies in healthcare workers. Vaccines 9(6):672. https://doi.org/10.3390/vaccines9060672
doi: 10.3390/vaccines9060672 pubmed: 34207300 pmcid: 8234791
Oosting SF, van der Veldt AAM, GeurtsvanKessel CH et al (2021) mRNA-1273 COVID-19 vaccination in patients receiving chemotherapy, immunotherapy, or chemoimmunotherapy for solid tumours: a prospective, multicentre, non-inferiority trial. Lancet Oncol 22(12):1681–1691. https://doi.org/10.1016/S1470-2045(21)00574-X
doi: 10.1016/S1470-2045(21)00574-X pubmed: 34767759 pmcid: 8577843
Tan CW, Chia WN, Qin X et al (2021) A SARS-CoV-2 surrogate virus neutralization test based on antibody-mediated blockage of ACE2-spike protein-protein interaction. Nat Biotechnol 38(9):1073–1078. https://doi.org/10.1038/s41587-020-0631-z
doi: 10.1038/s41587-020-0631-z
Wu JT, La J, Branch-Elliman W et al (2021) Association of COVID-19 vaccination with SARS-CoV-2 infection in patients with cancer: a US nationwide veterans affairs study. JAMA Oncol. https://doi.org/10.1001/jamaoncol.2021.5771
doi: 10.1001/jamaoncol.2021.5771 pubmed: 34554208 pmcid: 8640949
Barkoff AM, Knuutila A, Mertsola J et al (2021) Evaluation of anti-PT antibody response after pertussis vaccination and infection: the importance of both quantity and quality. Toxins (Basel) 13(8):508. https://doi.org/10.3390/toxins13080508
doi: 10.3390/toxins13080508 pubmed: 34437379
Tschismarov R, Zellweger RM, Koh MJ et al (2021) Antibody effector analysis of prime versus prime-boost immunizations with a recombinant measles-vectored chikungunya virus vaccine. JCI Insight 6(21):e151095. https://doi.org/10.1172/jci.insight.151095
doi: 10.1172/jci.insight.151095 pubmed: 34582377 pmcid: 8663552
Sisteré-Oró M, Wortmann DDJ, Andrade N et al (2022) Brief research report: anti-SARS-CoV-2 immunity in long lasting responders to cancer immunotherapy through mrna-based COVID-19 vaccination. Front Immunol 13:908108. https://doi.org/10.3389/fimmu.2022.908108
doi: 10.3389/fimmu.2022.908108 pubmed: 35911701 pmcid: 9330498

Auteurs

Teresita Caruso (T)

Clinical Immunology and Allergy Unit, Department of Clinical and Experimental Medicine, University of Pisa, Via Roma, 67, 56126, Pisa, Italy.

Francesca Salani (F)

Oncology Unit, Azienda Ospedaliera Universitaria Pisana, Pisa, Italy.
Sant'Anna School of Advanced Studies, Pisa, Italy.

Silvia Catanese (S)

Department of Translational Medicine and New Technologies for Medicine and Surgery, University of Pisa, Pisa, Italy.

Federico Pratesi (F)

Clinical Immunology and Allergy Unit, Department of Clinical and Experimental Medicine, University of Pisa, Via Roma, 67, 56126, Pisa, Italy.

Chiara Mercinelli (C)

Oncology Unit, Azienda Ospedaliera Universitaria Pisana, Pisa, Italy.

Giuseppe Motta (G)

Clinical Immunology and Allergy Unit, Department of Clinical and Experimental Medicine, University of Pisa, Via Roma, 67, 56126, Pisa, Italy.

Virginia Genovesi (V)

Oncology Unit, Azienda Ospedaliera Universitaria Pisana, Pisa, Italy.

Adele Bonato (A)

Oncology Unit, Azienda Ospedaliera Universitaria Pisana, Pisa, Italy.

Galimberti Sara (G)

Hematology Unit, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.

Gianluca Masi (G)

Department of Translational Medicine and New Technologies for Medicine and Surgery, University of Pisa, Pisa, Italy.

Paola Migliorini (P)

Clinical Immunology and Allergy Unit, Department of Clinical and Experimental Medicine, University of Pisa, Via Roma, 67, 56126, Pisa, Italy. paola.migliorini@unipi.it.

Articles similaires

[Redispensing of expensive oral anticancer medicines: a practical application].

Lisanne N van Merendonk, Kübra Akgöl, Bastiaan Nuijen
1.00
Humans Antineoplastic Agents Administration, Oral Drug Costs Counterfeit Drugs

Smoking Cessation and Incident Cardiovascular Disease.

Jun Hwan Cho, Seung Yong Shin, Hoseob Kim et al.
1.00
Humans Male Smoking Cessation Cardiovascular Diseases Female
Humans United States Aged Cross-Sectional Studies Medicare Part C
1.00
Humans Yoga Low Back Pain Female Male

Classifications MeSH