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We investigated Modified Vaccinia Ankara (MVA) vaccine candidates expressing the SARS\u2010CoV\u20101 or SARS\u2010CoV\u20102 Spike for their ability to induce antibodies targeting different epitopes on the SARS\u2010CoV\u20102 Receptor Binding Domain (RBD), including those with wide variant conservation. We also explored the capacity of these different Spike proteins to induce broad cross\u2010reactive or cross\u2010neutralizing B cells\u00a0against multiple variants. This revealed that the SARS\u2010CoV\u20101 Spike induced distinct patterns of epitope dominance compared to the traditional SARS\u2010CoV\u20102 Spike antigens. Following immune imprinting by previous exposure to ancestral SARS\u2010CoV\u20102 Spike, the epitope dominance patterns induced by SARS\u2010CoV\u20101 and SARS\u2010CoV\u20102 vaccines still differed, with most of the germinal center response consisting of\n                    <jats:italic>de novo<\/jats:italic>\n                    recruited B cells. In addition to the\n                    <jats:italic>de novo<\/jats:italic>\n                    response, B cells with germline cross\u2010reactivity to both antigens further increased their binding toward the most recently immunized antigen. Interestingly, we found that, while SARS\u2010CoV\u20102 vaccinated animals were extremely capable of mounting an antigen\u2010specific germinal center and plasmablast response to a booster immunization with SARS\u2010CoV\u20101, SARS\u2010CoV\u20102 boosters were less capable of inducing SARS\u2010CoV\u20102 specific B cells following prior SARS\u2010CoV\u20101 vaccination. These findings have broad implications for the implementation of vaccine strategies against emerging coronavirus variants and potential future coronavirus spillover events. The implications stemming from a fundamental directionality of immune imprinting and epitope dominance may have wider implications for noncoronavirus antigens.\n                  <\/jats:p>","DOI":"10.1111\/imcb.70072","type":"journal-article","created":{"date-parts":[[2026,1,6]],"date-time":"2026-01-06T13:19:28Z","timestamp":1767705568000},"page":"150-167","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Humoral epitope dominance and immune imprinting by\n                    <scp>SARS<\/scp>\n                    \u2010\n                    <scp>CoV<\/scp>\n                    \u20101 and\n                    <scp>SARS<\/scp>\n                    \u2010\n                    <scp>CoV<\/scp>\n                    \u20102 vaccines"],"prefix":"10.1111","volume":"104","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5642-3315","authenticated-orcid":false,"given":"Deborah 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