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These previous exposures can shape future immune responses and the ability to either recall memory B cells or generate\n                      <jats:italic toggle=\"yes\">de novo<\/jats:italic>\n                      immune responses. Therefore, it is important to consider pre-existing immunity when testing vaccine candidates. The B\/Victoria (B\/VIC) and the B\/Yamagata (B\/YAM) lineages circulated in the human population between 1987 and 2020 until the B\/YAM lineage stopped circulating following the coronavirus disease 2019 pandemic. Most people born prior to 2020 have pre-existing immune responses to both lineages of IBV. Therefore, in this report, the impact of vaccine-induced antibodies was explored in mice with pre-existing immune responses to B\/YAM or B\/VIC viruses alone or in combination. The recalled B cell responses induced by modern wild-type hemagglutinin (HA) vaccines from each IBV lineage were compared to the recalled B cell responses elicited by a broadly reactive antigen, B-COBRA-2 (BC2) HA, which elicits cross-lineage neutralizing antibodies. This report highlights the lineage specificity of immunological imprinting with IBV and demonstrates the antigen-specific activation of antibody-secreting B cells by broadly reactive antigens.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>IMPORTANCE<\/jats:title>\n                    <jats:p>This report demonstrates how varying immunological backgrounds to influenza B virus influence vaccine-induced responses in mice. It further highlights that a broadly reactive influenza B virus hemagglutinin (HA) antigen stimulates higher levels of IgM-secreting cells compared to wild-type HA antigens.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/jvi.00705-25","type":"journal-article","created":{"date-parts":[[2025,7,15]],"date-time":"2025-07-15T13:00:25Z","timestamp":1752584425000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":6,"title":["Breadth of antibody activity elicited by an influenza B hemagglutinin vaccine is influenced by pre-existing immune responses to influenza B viruses"],"prefix":"10.1128","volume":"99","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4077-7386","authenticated-orcid":false,"given":"Michael A.","family":"Carlock","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00te3t702","id-type":"ROR","asserted-by":"publisher"}],"name":"Center for Vaccines and Immunology, University of Georgia","place":["Athens, USA"]},{"name":"Florida Research and Innovation Center, Cleveland Clinic","place":["Port Saint Lucie, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Spencer R.","family":"Pierce","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00te3t702","id-type":"ROR","asserted-by":"publisher"}],"name":"Center for Vaccines and Immunology, University of Georgia","place":["Athens, USA"]},{"name":"Florida Research and Innovation Center, Cleveland Clinic","place":["Port Saint Lucie, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1947-7469","authenticated-orcid":true,"given":"Ted M.","family":"Ross","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00te3t702","id-type":"ROR","asserted-by":"publisher"}],"name":"Center for Vaccines and Immunology, University of Georgia","place":["Athens, USA"]},{"name":"Florida Research and Innovation Center, Cleveland Clinic","place":["Port Saint Lucie, USA"]},{"id":[{"id":"https:\/\/ror.org\/00te3t702","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Infectious Diseases, University of Georgia","place":["Athens, USA"]},{"id":[{"id":"https:\/\/ror.org\/03xjacd83","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Infection Biology, Lerner Research Institute, Cleveland Clinic","place":["Cleveland, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiy696"},{"key":"e_1_3_5_3_2","volume-title":"Cellular and molecular immunology","author":"Abbas AK","year":"2018","unstructured":"Abbas AK, Andrew HL, Pillai S. 2018. 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