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Vaccines can prevent these complications, but conserved non-neutralizing epitopes in the viral capsid may limit their effectiveness. The immunodominant PALXAXETG motif, located in the VP1 N-terminus, is a highly conserved region in enteroviruses that elicits non-neutralizing antibody responses. Virus-like particles (VLPs) offer a safe and effective vaccine platform because of their structural similarity to native viruses but lack viral genetic material. Importantly, VLPs can be structurally modified to exclude specific epitopes.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>Here, we produced a modified CVB1 virus-like particle (VLP) vaccine lacking 15 amino acids from the PALXAXETG motif (designated VLP\u0394palxa) using the baculovirus-insect cell expression system. To confirm the structural integrity, we determined the crystal structure of the modified VLP with 3.2\u00a0\u00c5 resolution. We then conducted comprehensive immunogenicity studies in mice, including dose titration, comparison of two versus three immunizations, and post-vaccination viral challenge. In addition, we evaluated the impact of the AS04 adjuvant on the immunogenicity of unmodified and modified CVB1-VLP vaccines and the formalin-inactivated CVB1 vaccine.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>The yield of CVB1-VLP\u0394palxa was 29.5\u00a0mg\/L, and the particles were shown to assemble similarly to unmodified CVB1-VLP. CVB1-VLP\u0394palxa induced robust antibody responses, with neutralizing antibody titres comparable to or exceeding those elicited by unmodified VLP or inactivated virus vaccines. A 2\u00a0\u00b5g dose was identified as optimal, providing the highest neutralizing antibody titres. A third immunization significantly increased antibody levels, and all non-adjuvanted vaccines protected the mice from CVB1 challenge after the third dose. The addition of AS04 significantly enhanced the antibody response, particularly in both VLP groups.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>We demonstrated that with targeted structural modification of the CVB1-VLP capsid, immunodominant antibody responses against the conserved PALXAXETG motif can be avoided. We demonstrate that structural modification of CVB1-VLP is a viable strategy. Since the deleted epitope is known to be non-neutralizing, its deletion may help focus the immune response on more protective targets and thereby improve vaccine efficacy. The modified VLPs, particularly when adjuvanted, offer a promising approach for developing safe and effective enterovirus vaccines.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Graphical Abstract<\/jats:title>\n          <\/jats:sec>","DOI":"10.1186\/s12929-025-01183-1","type":"journal-article","created":{"date-parts":[[2025,9,8]],"date-time":"2025-09-08T14:02:48Z","timestamp":1757340168000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Coxsackie B1 virus-like particle vaccine modified to exclude a highly conserved immunoreactive region from the capsid induces potent neutralizing antibodies and protects against infection in mice"],"prefix":"10.1186","volume":"32","author":[{"given":"Saana","family":"Soppela","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mart\u00edn","family":"Gonz\u00e1lez-Rodr\u00edguez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Virginia M.","family":"Stone","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Iiris","family":"Mustonen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Niila V. 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The procedures were approved by the Regional State Administrative Agency, Pirkanmaa, Finland (decision number ESAVI\/1408\/2021) or by the Stockholm Southern Animal Ethics Board. All animal reporting was conducted in accordance with ARRIVE guidelines. All efforts were made to minimize animal suffering and reduce the number of animals used. The welfare of the animals was monitored throughout the experiments.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"SS, NVVJ and MMH are inventors of the patent application FI 20253217 belonging to Innofend Oy, titled Engineered Enterovirus-Like particles and uses thereof. The rights to the invention have been transferred to the company, and thus, no competing interests exist. SS and MMH are shareholders of Innofend Oy. The other authors declare that they have no conflicts of interest.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"86"}}