{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,17]],"date-time":"2026-05-17T00:29:06Z","timestamp":1778977746359,"version":"3.51.4"},"reference-count":11,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,11,4]],"date-time":"2021-11-04T00:00:00Z","timestamp":1635984000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,11,4]],"date-time":"2021-11-04T00:00:00Z","timestamp":1635984000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100003196","name":"Ministero della Salute","doi-asserted-by":"publisher","award":["COVID-2020-12371735"],"award-info":[{"award-number":["COVID-2020-12371735"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003196","name":"Ministero della Salute","doi-asserted-by":"publisher","award":["RC Linea 1"],"award-info":[{"award-number":["RC Linea 1"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003196","name":"Ministero della Salute","doi-asserted-by":"publisher","award":["COVID-2020-12371817"],"award-info":[{"award-number":["COVID-2020-12371817"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["npj Vaccines"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Here we report on the humoral and cellular immune response in eight volunteers who autonomously chose to adhere to the Italian national COVID-19 vaccination campaign more than 3 months after receiving a single-administration GRAd-COV2 vaccine candidate in the context of the phase-1 clinical trial. We observed a clear boost of both binding\/neutralizing antibodies as well as T-cell responses upon receipt of the heterologous BNT162b2 or ChAdOx1-nCOV19 vaccines. These results, despite the limitation of the small sample size, support the concept that a single dose of an adenoviral vaccine may represent an ideal tool to effectively prime a balanced immune response, which can be boosted to high levels by a single dose of a different vaccine platform.<\/jats:p>","DOI":"10.1038\/s41541-021-00394-5","type":"journal-article","created":{"date-parts":[[2021,11,4]],"date-time":"2021-11-04T07:37:43Z","timestamp":1636011463000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Strong immunogenicity of heterologous prime-boost immunizations with the experimental vaccine GRAd-COV2 and BNT162b2 or ChAdOx1-nCOV19"],"prefix":"10.1038","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5252-0927","authenticated-orcid":false,"given":"Chiara","family":"Agrati","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2272-120X","authenticated-orcid":false,"given":"Stefania","family":"Capone","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9819-236X","authenticated-orcid":false,"given":"Concetta","family":"Castilletti","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eleonora","family":"Cimini","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giulia","family":"Matusali","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Silvia","family":"Meschi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eleonora","family":"Tartaglia","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roberto","family":"Camerini","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simone","family":"Lanini","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefano","family":"Milleri","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefano","family":"Colloca","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessandra","family":"Vitelli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonella","family":"Folgori","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,11,4]]},"reference":[{"key":"394_CR1","doi-asserted-by":"publisher","unstructured":"Pormohammad, A. et al. Efficacy and safety of COVID-19 vaccines: a systematic review and meta-analysis of randomized clinical trials. Vaccines, https:\/\/doi.org\/10.3390\/vaccines9050467 (2021).","DOI":"10.3390\/vaccines9050467"},{"key":"394_CR2","doi-asserted-by":"publisher","unstructured":"Wolff, J. et al. Ethical and policy considerations for COVID-19 vaccination modalities: delayed second dose, fractional dose, mixed vaccines. BMJ Glob. Health, https:\/\/doi.org\/10.1136\/bmjgh-2021-005912 (2021).","DOI":"10.1136\/bmjgh-2021-005912"},{"key":"394_CR3","doi-asserted-by":"publisher","first-page":"346","DOI":"10.1016\/j.coi.2009.05.016","volume":"21","author":"S Lu","year":"2009","unstructured":"Lu, S. Heterologous prime-boost vaccination. Curr. Opin. Immunol. 21, 346\u2013351 (2009).","journal-title":"Curr. Opin. Immunol."},{"key":"394_CR4","doi-asserted-by":"publisher","first-page":"1187","DOI":"10.1093\/infdis\/jiy639","volume":"219","author":"N Venkatraman","year":"2019","unstructured":"Venkatraman, N. et al. Safety and immunogenicity of a heterologous prime-boost ebola virus vaccine regimen in healthy adults in the United Kingdom and Senegal. J. Infect. Dis. 219, 1187\u20131197 (2019).","journal-title":"J. Infect. Dis."},{"key":"394_CR5","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1016\/j.omto.2020.10.001","volume":"19","author":"SS Ring","year":"2020","unstructured":"Ring, S. S. et al. Heterologous prime boost vaccination induces protective melanoma-specific CD8(+) T cell responses. Mol. Ther. Oncolytics 19, 179\u2013187 (2020).","journal-title":"Mol. Ther. Oncolytics"},{"key":"394_CR6","doi-asserted-by":"publisher","first-page":"629","DOI":"10.1080\/22221751.2021.1902245","volume":"10","author":"Q He","year":"2021","unstructured":"He, Q. et al. Heterologous prime-boost: breaking the protective immune response bottleneck of COVID-19 vaccine candidates. Emerg. Microbes Infect. 10, 629\u2013637 (2021).","journal-title":"Emerg. Microbes Infect."},{"key":"394_CR7","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-23173-1","volume":"12","author":"AJ Spencer","year":"2021","unstructured":"Spencer, A. J. et al. Heterologous vaccination regimens with self-amplifying RNA and adenoviral COVID vaccines induce robust immune responses in mice. Nat. Commun. 12, 2893 (2021).","journal-title":"Nat. Commun."},{"key":"394_CR8","unstructured":"Lanini, S. et al. GRAd-COV2, a gorilla adenovirus based candidate vaccine against COVID-19, is safe and immunogenic in young and older adults. Sci Transl Med. in press."},{"key":"394_CR9","first-page":"S2213","volume":"12","author":"D Hillus","year":"2021","unstructured":"Hillus, D. et al. Safety, reactogenicity, and immunogenicity of homologous and heterologous prime-boost immunisation with ChAdOx1-nCoV19 and BNT162b2: a prospective cohort study. Lancet Respir. Med. 12, S2213\u2013S2600 (2021).","journal-title":"Lancet Respir. Med."},{"key":"394_CR10","doi-asserted-by":"publisher","first-page":"856","DOI":"10.1016\/S0140-6736(21)01694-9","volume":"398","author":"X Liu","year":"2021","unstructured":"Liu, X. et al. Safety and immunogenicity report from the Com-COV study \u2013 a single-blind randomised non-inferiority trial comparing heterologous and homologous prime-boost schedules with an adenoviral vectored and mRNA COVID-19 vaccine. Lancet 398, 856\u2013869 (2021).","journal-title":"Lancet"},{"key":"394_CR11","doi-asserted-by":"publisher","unstructured":"Alter, G. et al. Immunogenicity of Ad26.COV2.S vaccine against SARS-CoV-2 variants in humans. Nature, https:\/\/doi.org\/10.1038\/s41586-021-03681-2 (2021).","DOI":"10.1038\/s41586-021-03681-2"}],"container-title":["npj Vaccines"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41541-021-00394-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41541-021-00394-5","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41541-021-00394-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,2]],"date-time":"2022-12-02T18:21:03Z","timestamp":1670005263000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41541-021-00394-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,11,4]]},"references-count":11,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["394"],"URL":"https:\/\/doi.org\/10.1038\/s41541-021-00394-5","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2021.06.22.21258961","asserted-by":"object"}]},"ISSN":["2059-0105"],"issn-type":[{"value":"2059-0105","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,11,4]]},"assertion":[{"value":"12 June 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"5 October 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 November 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"S.C., R.C., S.Co., A.V. and A.F. are employees of ReiThera Srl. S.Co. and AF are also shareholders of Keires AG. S.Co. and A.V. are inventors of the Patent Application No. 20183515.4 titled \u201cGORILLA ADENOVIRUS NUCLEIC ACID- AND AMINO ACID-SEQUENCES, VECTORS CONTAINING SAME, AND USES THEREOF\u201d. All remaining authors declare that they have no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"131"}}