{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T15:56:20Z","timestamp":1787500580679,"version":"build-2736575974"},"reference-count":39,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2025,9,30]],"date-time":"2025-09-30T00:00:00Z","timestamp":1759190400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000265","name":"MRC","doi-asserted-by":"publisher","award":["MR\/N013840\/1"],"award-info":[{"award-number":["MR\/N013840\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"name":"UK Department of Health and Social Care (DHSC) through an SBRI program managed by Innovate UK","award":["971556"],"award-info":[{"award-number":["971556"]}]}],"content-domain":{"domain":["www.mdpi.com"],"crossmark-restriction":true},"short-container-title":["Vaccines"],"abstract":"<jats:p>Background: The global health burden of mosquito-borne viruses, including dengue, yellow fever, Zika, and chikungunya, is rising due to climate change and globalisation, which favour mosquito habitat expansion. The genetic diversity of these viruses complicates the development of virus-specific vaccines or antivirals, highlighting the need for pan-viral strategies. As the common vector for these pathogens, mosquitoes and specifically their salivary proteins represent a promising target for such interventions. Mosquito saliva, secreted into the skin during biting, has immunomodulatory effects that can enhance host susceptibility to infection, but these mechanisms are not well defined in humans. Methods: The objective of this study was to determine whether AGS-v PLUS, a vaccine targeting mosquito salivary antigens, could modulate the human skin immune response to mosquito biting and potentially promote antiviral bystander immunity. In a Phase I trial, healthy volunteers were vaccinated with AGS-v PLUS (with or without adjuvant) or placebo, and three weeks later, they were exposed to bites from Aedes albopictus and Aedes aegypti mosquitoes. Skin biopsies from bitten and unbitten sites were analysed by transcriptomic profiling. Results: In placebo recipients, mosquito biting elicited a marked adaptive immune response at 48 h, characterised by CD4+ Th1 and CD8+ T cell signatures and leukocyte recruitment. While responses to Ae. aegypti and Ae. albopictus bites were broadly similar, those to Ae. albopictus were stronger. Vaccination with AGS-v PLUS, particularly with adjuvant, enhanced Th1 and CD8+ T cell-associated gene expression while suppressing pathways linked to neutrophilic inflammation and epithelial stress, which together may provide enhanced antiviral capacity. Conclusions: These findings demonstrate that targeting the host response to mosquito saliva via vaccination can reprogram the skin\u2019s immune response to mosquito bites, supporting a novel and broadly applicable pan-viral strategy to mitigate the impact of arboviral diseases.<\/jats:p>","DOI":"10.3390\/vaccines13101026","type":"journal-article","created":{"date-parts":[[2025,9,30]],"date-time":"2025-09-30T15:38:55Z","timestamp":1759246735000},"page":"1026","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["AGS-v PLUS, a Mosquito Salivary Peptide Vaccine, Modulates the Response to Aedes Mosquito Bites in Humans"],"prefix":"10.3390","volume":"13","author":[{"given":"Liam","family":"Barningham","sequence":"first","affiliation":[{"name":"School of Medicine, University of Leeds, Welcome Trust Brenner Building, St. James\u2019 University Hospital, Beckett Street, Leeds LS9 7TF, UK"},{"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\/0000-0001-9544-1068","authenticated-orcid":false,"given":"Ian M.","family":"Carr","sequence":"additional","affiliation":[{"name":"School of Medicine, University of Leeds, Welcome Trust Brenner Building, St. James\u2019 University Hospital, Beckett Street, Leeds LS9 7TF, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Si\u00e2n","family":"Jossi","sequence":"additional","affiliation":[{"name":"Heyford Park Innovation Centre, ConserV Bioscience Ltd., 77 Heyford Park, 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":"Heyford Park Innovation Centre, ConserV Bioscience Ltd., 77 Heyford Park, Bicester OX25 5HD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aiyana","family":"Ponce","sequence":"additional","affiliation":[{"name":"Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mara","family":"Short","sequence":"additional","affiliation":[{"name":"Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852, USA"},{"name":"Department of Entomology, College of Agriculture, Life, and Environmental Sciences, University of Arizona, Tucson, AZ 85721-0036, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudio","family":"Meneses","sequence":"additional","affiliation":[{"name":"Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9956-8039","authenticated-orcid":false,"given":"Joshua R.","family":"Lacsina","sequence":"additional","affiliation":[{"name":"Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5589-9450","authenticated-orcid":false,"given":"Jesus G.","family":"Valenzuela","sequence":"additional","affiliation":[{"name":"Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7924-8038","authenticated-orcid":false,"given":"Fabiano","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3874-581X","authenticated-orcid":false,"given":"Matthew B.","family":"Laurens","sequence":"additional","affiliation":[{"name":"Center for Vaccine Development and Global Health, University of Maryland School of Medicine, 685 W Baltimore St Room 480, Baltimore, MD 21201-1509, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0373-4643","authenticated-orcid":false,"given":"DeAnna J.","family":"Friedman-Klabanoff","sequence":"additional","affiliation":[{"name":"Center for Vaccine Development and Global Health, University of Maryland School of Medicine, 685 W Baltimore St Room 480, Baltimore, MD 21201-1509, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7099-5002","authenticated-orcid":false,"given":"Olga","family":"Pleguezuelos","sequence":"additional","affiliation":[{"name":"Heyford Park Innovation Centre, ConserV Bioscience Ltd., 77 Heyford Park, Bicester OX25 5HD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucy F.","family":"Stead","sequence":"additional","affiliation":[{"name":"School of Medicine, University of Leeds, Welcome Trust Brenner Building, St. James\u2019 University Hospital, Beckett Street, Leeds LS9 7TF, UK"}],"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":"School of Medicine, University of Leeds, Welcome Trust Brenner Building, St. James\u2019 University Hospital, Beckett Street, Leeds LS9 7TF, UK"},{"name":"Virus Host Interaction Team, Skin Research Centre, Hull York Medical School, University of York, York YO10 5DD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1146\/annurev-virology-110615-035630","article-title":"Climate Change and the Arboviruses: Lessons from the Evolution of the Dengue and Yellow Fever Viruses","volume":"3","author":"Tabachnick","year":"2016","journal-title":"Annu. 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