{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T06:15:35Z","timestamp":1778652935238,"version":"3.51.4"},"reference-count":32,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T00:00:00Z","timestamp":1778630400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002855","name":"Ministry of Science and Technology of the People's Republic of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002855","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Coxsackievirus A5 (CV-A5) has re-emerged as an important pathogen associated with hand, foot, and mouth disease (HFMD) in young children. However, the antigenic structure of CV-A5 and the key determinants responsible for neutralizing antibody responses remain largely undefined, hindering rational vaccine design and antibody-based intervention strategies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>To investigate the relationship between viral particle composition and humoral immune responses, three forms of CV-A5 particles, including empty particles (EPs), full particles (FPs), A-particles (APs) were purified from the candidate vaccine strain CV-A5-3487, and artificial B-particles (BPs) were generated by heat treatment of FPs. These four particles were evaluated in mice. A mouse-adapted strain (CV-A5-611) was used to mimic natural infection for monoclonal antibody generation, and neutralizing hybridomas were rapidly screened using a fluorescent reporter virus (CV-A5-r611-iLOV). Linear epitope mapping was performed using truncated peptides and alanine scanning peptides, followed by sequence conservation analysis. Protective efficacy of the neutralizing antibody was evaluated in a lethal mouse challenge model.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Among the four particle types, FPs elicited the most potent neutralizing antibody responses, indicating that intact virions are critical for inducing effective humoral immunity. Hybridoma screening generated 617 ELISA-positive clones, of which 84 (13.61%) exhibited neutralizing activity against CV-A5. Ten neutralizing monoclonal antibodies (mAb) were obtained after subcloning, and only one antibody, 4D6, recognized a linear epitope. Epitope mapping identified the binding site within VP1 residues 155-169 (VPPGAPVPTGRDTFQ), with the minimal neutralizing core epitope defined as 158GAPVPTGR165. This epitope showed high sequence conservation (90.5%) among CV-A5 strains, suggesting a structurally constrained neutralization site. Passive transfer experiments demonstrated that mAb 4D6 conferred complete protection against lethal CV-A5 challenge at a dose of 20 \u03bcg per mouse, confirming its strong\n                      <jats:italic>in vivo<\/jats:italic>\n                      protective activity.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our study provides a systematic comparison of the immunogenicity of distinct CV-A5 particle forms and identifies a highly conserved linear neutralizing epitope on VP1 for the first time. The potent protective efficacy of mAb 4D6 highlights the importance of this epitope as a target for therapeutic antibody development and rational vaccine design, and provides new insights into the mechanisms of protective humoral immunity against CV-A5 infection.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1837529","type":"journal-article","created":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T05:54:29Z","timestamp":1778651669000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Antigenic characterization and mapping of a conserved neutralizing epitope on VP1 of coxsackievirus A5"],"prefix":"10.3389","volume":"17","author":[{"given":"Chen","family":"Wang","sequence":"first","affiliation":[{"name":"Wuhan Institute of Biological Products Co., Ltd.","place":["Wuhan, China"]},{"name":"Hubei Provincial Vaccines Technology Innovation Center","place":["Wuhan, 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