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Current prophylactic measures, mainly serovar-specific bacterins administered to sows, are limited by maternal immunity, which can interfere with active immunization in piglets. Subunit vaccines containing\n                      <jats:italic>G. parasuis<\/jats:italic>\n                      -specific antigenic molecules show promise but are not yet commercially available. Transferrin-binding proteins (Tbp), which enable\n                      <jats:italic>G. parasuis<\/jats:italic>\n                      to acquire iron in low-iron environments like mucosal surfaces, have been proposed as potential vaccine antigens. The mucosal administration of a TbpB-based subunit vaccine could provide a promising solution to overcome the limitations posed by maternal immunity, offering an effective approach to control the disease in weaning piglets. This study, conducted in two phases, primarily evaluates (days 0\u201345) the immunogenicity of a two-dose oral mucosal TbpB-based subunit vaccine (TbpB\n                      <jats:sup>Y167A<\/jats:sup>\n                      ) administered to colostrum-deprived piglets, and subsequently (days 45\u201352), its heterologous protection by challenging these piglets with four\n                      <jats:italic>G. parasuis<\/jats:italic>\n                      clinical isolates from different TbpB clusters (I, III) and serovars (SV1, SV4, SV5, SV7) recovered from Spanish pig farms.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The oral mucosal administration of the two-dose TbpB-based vaccine induced a robust humoral immune response in immunized colostrum-deprived piglets, significantly increasing IgA and IgM concentration 15\u00a0days after the second dose (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.01). Upon challenge with four\n                      <jats:italic>G. parasuis<\/jats:italic>\n                      clinical isolates, the vaccine demonstrated heterologous protection, markedly improving survival rates (OR: 8.45; CI 95%: 4.97\u201314.36) and significantly reducing clinical signs and lesions, regardless of the TbpB cluster and serovar. The vaccine reduced\n                      <jats:italic>G. parasuis<\/jats:italic>\n                      colonization in the respiratory tract (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.0001) and\n                      <jats:italic>G. parasuis<\/jats:italic>\n                      systemic target tissues, like tarsus and carpus joints, liver, and brain (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.05). Immunohistochemical analysis showed a lower macrophage count in different lung locations of immunized piglets (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.0001).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      This study demonstrates that oral mucosal administration of the TbpB\n                      <jats:sup>Y167A<\/jats:sup>\n                      subunit vaccine in piglets provides effective heterologous protection against diverse virulent European\n                      <jats:italic>G. parasuis<\/jats:italic>\n                      field isolates, significantly reducing bacterial colonization and dissemination. This vaccine offers a promising alternative to traditional bacterins, overcoming limitations due to maternal immunity, and represents a strong candidate for universal vaccination against Gl\u00e4sser\u2019s disease.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s40813-024-00404-7","type":"journal-article","created":{"date-parts":[[2024,11,28]],"date-time":"2024-11-28T09:57:52Z","timestamp":1732787872000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["TbpB-based oral mucosal vaccine provides heterologous protection against Gl\u00e4sser\u2019s disease caused by different serovars of Spanish field isolates of Glaesserella parasuis"],"prefix":"10.1186","volume":"10","author":[{"given":"Alba","family":"Gonz\u00e1lez-Fern\u00e1ndez","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oscar","family":"Menc\u00eda-Ares","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda Jos\u00e9","family":"Garc\u00eda-Iglesias","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u00e1ximo","family":"Petrocchi-Rilo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rub\u00e9n","family":"Migu\u00e9lez-P\u00e9rez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"Perell\u00f3-Jim\u00e9nez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Herencia-Lagunar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vanessa","family":"Acebes-Fern\u00e1ndez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e9sar B.","family":"Guti\u00e9rrez-Mart\u00edn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonia","family":"Mart\u00ednez-Mart\u00ednez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,11,28]]},"reference":[{"issue":"12","key":"404_CR1","doi-asserted-by":"publisher","first-page":"2711","DOI":"10.1128\/jcm.28.12.2711-2716.1990","volume":"28","author":"K Moller","year":"1990","unstructured":"Moller K, Kilian M. 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