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Mosquito saliva, secreted during biting, facilitates blood feeding and can enhance virus infection. Here, we evaluated whether combining virus-specific antigens with mosquito salivary protein-derived peptides improves protection in Zika virus (ZIKV) and chikungunya virus (CHIKV) mouse models. Methods: Peptides from Aedes and Culex salivary proteins were selected based on conservation, predicted T-cell reactivity, and cellular and humoral immunogenicity in mice. Mice were immunised subcutaneously with a prime and boost two weeks apart using adjuvanted salivary peptides (SAL), commercial ZIKV- or CHIKV-like particles (VLPs), or salivary peptides combined with the relevant VLPs. Vaccine doses contained 0.5 \u00b5g VLPs and\/or 10 nmol of each salivary peptide, formulated with Montanide ISA-51; when combined, VLPs and SAL were administered on opposite flanks. Two weeks after boosting, mice were challenged with ZIKV or CHIKV plus Aedes aegypti saliva. Challenge teams were blinded to group allocation until data analyses were complete. Results: SAL enhanced the protective effect of VLP vaccination compared with VLPs alone. In the CHIKV model, CHIKV VLP + SAL prevented joint swelling and reduced infectious virus in the inoculated ankle and viral RNA in the contralateral ankle. In the ZIKV model, ZIKV VLP + SAL reduced viral RNA in skin and brain tissue and improved survival. Conclusions: Mosquito salivary peptide antigens improved the protective efficacy of VLP vaccines against ZIKV and CHIKV in mouse models. Salivary antigens may provide a complementary vaccine component for multiple arboviruses transmitted by Aedes and Culex mosquitoes.<\/jats:p>","DOI":"10.3390\/vaccines14080723","type":"journal-article","created":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T14:20:36Z","timestamp":1787322036000},"page":"723","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Mosquito Saliva Subunit Vaccine Enhances Efficacy of VLP Vaccines Against Zika and Chikungunya Viruses"],"prefix":"10.3390","volume":"14","author":[{"given":"Si\u00e2n","family":"Jossi","sequence":"first","affiliation":[{"name":"ConserV Bioscience Ltd., Heyford Park Innovation Centre, Upper Heyford, Bicester OX25 5HD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5154-5786","authenticated-orcid":false,"given":"Megan","family":"Cole","sequence":"additional","affiliation":[{"name":"ConserV Bioscience Ltd., Heyford Park Innovation Centre, Upper Heyford, Bicester OX25 5HD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7955-086X","authenticated-orcid":false,"given":"Yonca","family":"Keskek Turk","sequence":"additional","affiliation":[{"name":"Virus Host Interaction Team, Skin Research Centre, Hull York Medical School, University of York, York YO10 5DD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9957-0307","authenticated-orcid":false,"given":"Sam","family":"Verwimp","sequence":"additional","affiliation":[{"name":"Laboratory of Virus-Host Interactions and Therapeutic Applications, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Katholieke Universiteit (KU) Leuven, 3000 Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katrien","family":"Trappeniers","sequence":"additional","affiliation":[{"name":"Laboratory of Virus-Host Interactions and Therapeutic Applications, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Katholieke Universiteit (KU) Leuven, 3000 Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Luk","sequence":"additional","affiliation":[{"name":"Department of Biology, University of York, York YO10 5DD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua X. D.","family":"Ang","sequence":"additional","affiliation":[{"name":"Department of Biology, University of York, York YO10 5DD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luke","family":"Alphey","sequence":"additional","affiliation":[{"name":"Department of Biology, University of York, York YO10 5DD, UK"},{"name":"York Biomedical Research Institute, University of York, York YO10 5DD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8874-675X","authenticated-orcid":false,"given":"Leen","family":"Delang","sequence":"additional","affiliation":[{"name":"Laboratory of Virus-Host Interactions and Therapeutic Applications, Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Katholieke Universiteit (KU) Leuven, 3000 Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7694-9509","authenticated-orcid":false,"given":"Clive S.","family":"McKimmie","sequence":"additional","affiliation":[{"name":"Virus Host Interaction Team, Skin Research Centre, Hull York Medical School, University of York, York YO10 5DD, UK"},{"name":"York Biomedical Research Institute, University of York, York YO10 5DD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7099-5002","authenticated-orcid":false,"given":"Olga","family":"Pleguezuelos","sequence":"additional","affiliation":[{"name":"ConserV Bioscience Ltd., Heyford Park Innovation Centre, Upper Heyford, Bicester OX25 5HD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,21]]},"reference":[{"key":"ref_1","unstructured":"WHO (2025, December 05). 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