{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T21:40:34Z","timestamp":1784756434697,"version":"3.55.0"},"reference-count":35,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T00:00:00Z","timestamp":1767830400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>\n                      <jats:italic>Clostridium perfringens<\/jats:italic>\n                      (\n                      <jats:italic>C. perfringens<\/jats:italic>\n                      ), a ubiquitous Gram-positive bacterium in the environment and mammalian gut flora, is a leading cause of enterotoxemia in animals, necrotizing enteritis in humans and animals, and gas gangrene in both, attributed to its diverse exotoxin profile. Alpha-toxin, a pivotal virulence factor produced by all\n                      <jats:italic>C. perfringens<\/jats:italic>\n                      serotypes, plays a central role in the pathogenicity of these diseases.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Here, we engineered a lipid nanoparticle encapsulated CPA-CTD mRNA vaccine targeting the conserved C-terminal domain of\n                      <jats:italic>C. perfringens<\/jats:italic>\n                      alpha-toxin and rigorously assessed its immunogenicity and protective efficacy in mouse and bovine models.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The CPA-CTD mRNA vaccine induced strong humoral and cellular immune responses in mice, particularly in promoting the rapid production of specific IgG and mucosal IgA antibodies, as well as enhancing T cell immune responses, surpassing conventional subunit vaccines. Protection was confirmed in dual challenge models --enterotoxemia and gas gangrene --where the vaccine provided complete immunity against lethal doses of alpha-toxin and\n                      <jats:italic>C. perfringens<\/jats:italic>\n                      infection. In cattle, the CPA-CTD mRNA vaccine induced high-titer IgG antibodies and toxin-neutralizing antibodies. Notably, immunization of pregnant cows led to efficient transfer of these antibodies via colostrum to newborn calves, providing passive protection.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>\n                      These results demonstrate that the CPA-CTD mRNA vaccine provides rapid and robust immune protection against\n                      <jats:italic>C. perfringens<\/jats:italic>\n                      alpha-toxin-associated diseases, with promising potential for applications in both veterinary and human health.\n                    <\/jats:p>\n                  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