{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T01:05:35Z","timestamp":1760231135912,"version":"build-2065373602"},"reference-count":19,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2022,8,30]],"date-time":"2022-08-30T00:00:00Z","timestamp":1661817600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Fondation pour la Recherche m\u00e9dicale (FRM)"},{"name":"ANR Flash COVID-19"},{"name":"ANRS maladies infectieuses emergentes"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Immunocompromised individuals generally fail to mount efficacious immune humoral responses following vaccination. The emergence of SARS-CoV-2 variants of concern has raised the question as to whether levels of anti-spike protein antibodies achieved after two or three doses of the vaccine efficiently protect against breakthrough infection in the context of immune suppression. We used a fluorescence-based neutralization assay to test the sensitivity of SARS-CoV-2 variants (ancestral variant, Beta, Delta, and Omicron BA.1) to the neutralizing response induced by vaccination in highly immunosuppressed allogeneic HSCT recipients, tested after two and three doses of the BNT162b2 vaccine. We show that neutralizing antibody responses to the Beta and Delta variants in most immunocompromised HSCT recipients increased after three vaccine doses up to values similar to those observed in twice-vaccinated healthy adults and were significantly lower against Omicron BA.1. Overall, neutralization titers correlated with the amount of anti-S-RBD antibodies measured by means of enzyme immunoassay, indicating that commercially available assays can be used to quantify the anti-S-RBD antibody response as a reliable surrogate marker of humoral immune protection in both immunocompetent and immunocompromised individuals. Our findings support the recommendation of additional early vaccine doses as a booster of humoral neutralizing activity against emerging variants, in HSCT immunocompromised patients. In the context of Omicron circulation, it further emphasizes the need for reinforcement of preventive measures including the administration of monoclonal antibodies in this high-risk population.<\/jats:p>","DOI":"10.3390\/v14091928","type":"journal-article","created":{"date-parts":[[2022,8,31]],"date-time":"2022-08-31T02:09:36Z","timestamp":1661911776000},"page":"1928","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Third Early \u201cBooster\u201d Dose Strategy in France of bnt162b2 SARS-CoV-2 Vaccine in Allogeneic Hematopoietic Stem Cell Transplant Recipients Enhances Neutralizing Antibody Responses"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6489-5091","authenticated-orcid":false,"given":"Abdelhakim","family":"Ahmed-Belkacem","sequence":"first","affiliation":[{"name":"University Paris Est Cr\u00e9teil, INSERM U955, IMRB, 94010 Creteil, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rabah","family":"Redjoul","sequence":"additional","affiliation":[{"name":"Haematology Department, Assistance Publique, H\u00f4pitaux de Paris, Henri Mondor Hospital, 94000 Creteil, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rozenn","family":"Brillet","sequence":"additional","affiliation":[{"name":"University Paris Est Cr\u00e9teil, INSERM U955, IMRB, 94010 Creteil, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nazim","family":"Ahnou","sequence":"additional","affiliation":[{"name":"University Paris Est Cr\u00e9teil, INSERM U955, IMRB, 94010 Creteil, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mathieu","family":"Leclerc","sequence":"additional","affiliation":[{"name":"University Paris Est Cr\u00e9teil, INSERM U955, IMRB, 94010 Creteil, France"},{"name":"Haematology Department, Assistance Publique, H\u00f4pitaux de Paris, Henri Mondor Hospital, 94000 Creteil, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6456-4521","authenticated-orcid":false,"given":"Dennis Salom\u00f3n","family":"L\u00f3pez-Molina","sequence":"additional","affiliation":[{"name":"University Paris Est Cr\u00e9teil, INSERM U955, IMRB, 94010 Creteil, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexandre","family":"Soulier","sequence":"additional","affiliation":[{"name":"Department of Virology, H\u00f4pital Henri Mondor, AP-HP, Universit\u00e9 Paris-Est, 94000 Creteil, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aur\u00e9lie","family":"Gourgeon","sequence":"additional","affiliation":[{"name":"Department of Virology, H\u00f4pital Henri Mondor, AP-HP, Universit\u00e9 Paris-Est, 94000 Creteil, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9817-5006","authenticated-orcid":false,"given":"Christophe","family":"Rodriguez","sequence":"additional","affiliation":[{"name":"University Paris Est Cr\u00e9teil, INSERM U955, IMRB, 94010 Creteil, France"},{"name":"Department of Virology, H\u00f4pital Henri Mondor, AP-HP, Universit\u00e9 Paris-Est, 94000 Creteil, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S\u00e9bastien","family":"Maury","sequence":"additional","affiliation":[{"name":"University Paris Est Cr\u00e9teil, INSERM U955, IMRB, 94010 Creteil, France"},{"name":"Haematology Department, Assistance Publique, H\u00f4pitaux de Paris, Henri Mondor Hospital, 94000 Creteil, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jean-Michel","family":"Pawlotsky","sequence":"additional","affiliation":[{"name":"University Paris Est Cr\u00e9teil, INSERM U955, IMRB, 94010 Creteil, France"},{"name":"Department of Virology, H\u00f4pital Henri Mondor, AP-HP, Universit\u00e9 Paris-Est, 94000 Creteil, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1236-5467","authenticated-orcid":false,"given":"Slim","family":"Fourati","sequence":"additional","affiliation":[{"name":"University Paris Est Cr\u00e9teil, INSERM U955, IMRB, 94010 Creteil, France"},{"name":"Department of Virology, H\u00f4pital Henri Mondor, AP-HP, Universit\u00e9 Paris-Est, 94000 Creteil, France"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,8,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2603","DOI":"10.1056\/NEJMoa2034577","article-title":"Safety and Efficacy of the BNT162b2 mRNA COVID-19 Vaccine","volume":"383","author":"Polack","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1056\/NEJMoa2035389","article-title":"Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine","volume":"384","author":"Baden","year":"2021","journal-title":"N. Engl. J. 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Med."},{"key":"ref_13","first-page":"322","article-title":"Efficiency of a boost with a third dose of anti-SARS-CoV-2 messenger RNA-based vaccines in solid organ transplant recipients","volume":"22","author":"Abravanel","year":"2021","journal-title":"Am. J. Transplant."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"917","DOI":"10.1038\/s41591-021-01318-5","article-title":"Sensitivity of infectious SARS-CoV-2 B.1.1.7 and B.1.351 variants to neutralizing antibodies","volume":"27","author":"Planas","year":"2021","journal-title":"Nat. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1038\/s41586-021-03693-y","article-title":"BNT162b2-elicited neutralization of B.1.617 and other SARS-CoV-2 variants","volume":"596","author":"Liu","year":"2021","journal-title":"Nature"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1038\/s41586-021-03944-y","article-title":"SARS-CoV-2 B.1.617.2 Delta variant replication and immune evasion","volume":"599","author":"Mlcochova","year":"2021","journal-title":"Nature"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1038\/s41586-021-03777-9","article-title":"Reduced sensitivity of SARS-CoV-2 variant Delta to antibody neutralization","volume":"596","author":"Planas","year":"2021","journal-title":"Nature"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"3094","DOI":"10.1038\/s41409-021-01466-9","article-title":"Antibody responses to SARS-CoV2 vaccination in allogeneic hematopoietic stem cell transplant recipients","volume":"56","author":"Mamez","year":"2021","journal-title":"Bone Marrow Transplant."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1038\/s41586-021-04389-z","article-title":"Considerable escape of SARS-CoV-2 Omicron to antibody neutralization","volume":"602","author":"Planas","year":"2022","journal-title":"Nature"}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/14\/9\/1928\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:20:38Z","timestamp":1760142038000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/14\/9\/1928"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,8,30]]},"references-count":19,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2022,9]]}},"alternative-id":["v14091928"],"URL":"https:\/\/doi.org\/10.3390\/v14091928","relation":{},"ISSN":["1999-4915"],"issn-type":[{"type":"electronic","value":"1999-4915"}],"subject":[],"published":{"date-parts":[[2022,8,30]]}}}