{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T02:27:21Z","timestamp":1760149641593,"version":"build-2065373602"},"reference-count":61,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2023,9,3]],"date-time":"2023-09-03T00:00:00Z","timestamp":1693699200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Danish Ministry of Education and Research","award":["0237-00006B"],"award-info":[{"award-number":["0237-00006B"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>The ideal vaccine against viral infections should elicit antibody responses that protect against divergent strains. Designing broadly protective vaccines against SARS-CoV-2 and other divergent viruses requires insight into the specific targets of cross-protective antibodies on the viral surface protein(s). However, unlike therapeutic monoclonal antibodies, the B-cell epitopes of vaccine-induced polyclonal antibody responses remain poorly defined. Here we show that, through the combination of neutralizing antibody functional responses with B-cell epitope mapping, it is possible to identify unique antibody targets associated with neutralization breadth. The polyclonal antibody profiles of SARS-CoV-2 index-strain-vaccinated rabbits that demonstrated a low, intermediate, or high neutralization efficiency of different SARS-CoV-2 variants of concern (VOCs) were distinctly different. Animals with an intermediate and high cross-neutralization of VOCs targeted fewer antigenic sites on the spike protein and targeted one particular epitope, subdomain 1 (SD1), situated outside the receptor binding domain (RBD). Our results indicate that a targeted functional antibody response and an additional focus on non-RBD epitopes could be effective for broad protection against different SARS-CoV-2 variants. We anticipate that the approach taken in this study can be applied to other viral vaccines for identifying future epitopes that confer cross-neutralizing antibody responses, and that our findings will inform a rational vaccine design for SARS-CoV-2.<\/jats:p>","DOI":"10.3390\/vaccines11091451","type":"journal-article","created":{"date-parts":[[2023,9,4]],"date-time":"2023-09-04T02:14:50Z","timestamp":1693793690000},"page":"1451","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["A Candidate DNA Vaccine Encoding the Native SARS-CoV-2 Spike Protein Induces Anti-Subdomain 1 Antibodies"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2841-7655","authenticated-orcid":false,"given":"Anders","family":"Frische","sequence":"first","affiliation":[{"name":"Department of Virus & Microbiological Special Diagnostics, Statens Serum Institut, 2300 Copenhagen, Denmark"},{"name":"Section of Molecular and Medicinal Biology, Department of Science and Environment, Roskilde University, 4000 Roskilde, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vithiagaran","family":"Gunalan","sequence":"additional","affiliation":[{"name":"Department of Virus & Microbiological Special Diagnostics, Statens Serum Institut, 2300 Copenhagen, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7536-3453","authenticated-orcid":false,"given":"Karen Angeliki","family":"Krogfelt","sequence":"additional","affiliation":[{"name":"Department of Virus & Microbiological Special Diagnostics, Statens Serum Institut, 2300 Copenhagen, Denmark"},{"name":"Section of Molecular and Medicinal Biology, Department of Science and Environment, Roskilde University, 4000 Roskilde, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anders","family":"Fomsgaard","sequence":"additional","affiliation":[{"name":"Department of Virus & Microbiological Special Diagnostics, Statens Serum Institut, 2300 Copenhagen, Denmark"},{"name":"Infectious Diseases Unit, Clinical Institute, University of Southern Denmark, 5230 Odense, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3910-7185","authenticated-orcid":false,"given":"Ria","family":"Lassauni\u00e8re","sequence":"additional","affiliation":[{"name":"Department of Virus & Microbiological Special Diagnostics, Statens Serum Institut, 2300 Copenhagen, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,9,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"4848","DOI":"10.1016\/j.cell.2021.08.017","article-title":"The origins of SARS-CoV-2: A critical review","volume":"184","author":"Holmes","year":"2021","journal-title":"Cell"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1038\/s41586-020-2012-7","article-title":"A pneumonia outbreak associated with a new coronavirus of probable bat origin","volume":"579","author":"Zhou","year":"2020","journal-title":"Nature"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"11727","DOI":"10.1073\/pnas.2003138117","article-title":"Cell entry mechanisms of SARS-CoV-2","volume":"117","author":"Shang","year":"2020","journal-title":"Proc. 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