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Despite the availability of efficacious vaccines, new variants with reduced sensitivity to vaccine\u2010induced protection are a troubling new reality. The Ad26.COV2.S vaccine is a recombinant, replication\u2010incompetent human adenovirus type 26 vector encoding a full\u2010length, membrane\u2010bound severe acute respiratory syndrome coronavirus 2 (SARS\u2010CoV\u20102) spike protein in a prefusion\u2010stabilized conformation. This review discusses the immunogenicity and efficacy of Ad26.COV2.S as a single\u2010dose primary vaccination and as a homologous or heterologous booster vaccination. Ad26.COV2.S elicits broad humoral and cellular immune responses, which are associated with protective efficacy\/effectiveness against SARS\u2010CoV\u20102 infection, moderate to severe\/critical COVID\u201019, and COVID\u201019\u2013related hospitalization and death, including against emerging SARS\u2010CoV\u20102 variants. The humoral immune responses elicited by Ad26.COV2.S vaccination are durable, continue to increase for at least 2\u20103\u00a0months postvaccination, and involve a range of functional antibodies. Ad26.COV2.S given as a heterologous booster to mRNA vaccine\u2013primed individuals markedly increases humoral and cellular immune responses. The use of Ad26.COV2.S as primary vaccination and as part of booster regimens is supporting the ongoing efforts to control and mitigate the COVID\u201019 pandemic.<\/jats:p>","DOI":"10.1111\/imr.13088","type":"journal-article","created":{"date-parts":[[2022,6,11]],"date-time":"2022-06-11T07:24:46Z","timestamp":1654932286000},"page":"47-60","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Immunogenicity and efficacy of Ad26.<scp>COV2<\/scp>.S: An adenoviral vector\u2013based <scp>COVID<\/scp>\u201019 vaccine"],"prefix":"10.1111","volume":"310","author":[{"given":"Mathieu","family":"Le Gars","sequence":"first","affiliation":[{"name":"Janssen Vaccines and Prevention  Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jenny","family":"Hendriks","sequence":"additional","affiliation":[{"name":"Janssen Vaccines and Prevention  Leiden The 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