{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:42:25Z","timestamp":1760060545406,"version":"build-2065373602"},"reference-count":43,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2025,8,30]],"date-time":"2025-08-30T00:00:00Z","timestamp":1756512000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institute of Health","doi-asserted-by":"publisher","award":["R01AI127744","R01 NS125778","R01 AI176670","U19AI181960-01"],"award-info":[{"award-number":["R01AI127744","R01 NS125778","R01 AI176670","U19AI181960-01"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"McLaughlin Predoctoral Fellowship at UTMB","award":["R01AI127744","R01 NS125778","R01 AI176670","U19AI181960-01"],"award-info":[{"award-number":["R01AI127744","R01 NS125778","R01 AI176670","U19AI181960-01"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>Eilat (EILV)\/chikungunya virus (CHIKV) is a chimeric virus that contains the nonstructural proteins and cis-acting sequences of EILV and the structural proteins of CHIKV. EILV\/CHIKV vaccination is known to protect with a single dose against wild-type (WT) CHIKV challenge in mice and non-human primates. The underlying immune mechanism of the vaccine-induced host protection remains unknown. \u03b3\u03b4 T cells react to WT CHIKV infection by controlling the virus-induced tissue inflammation and damage. Here, we found that \u03b3\u03b4 T cells contribute to EILV\/CHIKV-induced host protection against WT CHIKV infection. TCR\u03b4\u2212\/\u2212 mice, which are deficient of \u03b3\u03b4 T cells, had impaired CHIKV-specific CD8+ T cell responses, antibody production and memory B cell responses following vaccination. Both antibody and CD8+ T cells of EILV\/CHIKV-vaccinated mice were required for protection type I interferon receptor deficient mice from lethal WT CHIKV infection. Moreover, \u03b3\u03b4 T cells expanded quickly in response to EILV\/CHIKV vaccination. TCR\u03b4\u2212\/\u2212 mice, had lower levels of innate immune cytokines and impaired activation of antigen presenting cell (APCs). Overall, \u03b3\u03b4 T cells contribute to EILV\/CHIKV-induced host protection by promoting APC maturation, T cell priming and the induction of humoral immune responses upon EILV\/CHIKV vaccination.<\/jats:p>","DOI":"10.3390\/pathogens14090863","type":"journal-article","created":{"date-parts":[[2025,9,2]],"date-time":"2025-09-02T15:02:57Z","timestamp":1756825377000},"page":"863","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["\u03b3\u03b4 T Cells Mediate Protective Immunity Following Vaccination with an Insect-Based Chikungunya Fever Vaccine in Mice"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-1685-2891","authenticated-orcid":false,"given":"Leslie","family":"Rodriguez","sequence":"first","affiliation":[{"name":"Department of Microbiology & Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Awadalkareem","family":"Adam","sequence":"additional","affiliation":[{"name":"Department of Microbiology & Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA"},{"name":"Sealy Institute for Vaccine Sciences, University of Texas Medical Branch, Galveston, TX 77555, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0367-6888","authenticated-orcid":false,"given":"Huanle","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Microbiology & Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5011-3869","authenticated-orcid":false,"given":"Samantha R.","family":"Osman","sequence":"additional","affiliation":[{"name":"Department of Microbiology & Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7485-3167","authenticated-orcid":false,"given":"Kenneth","family":"Plante","sequence":"additional","affiliation":[{"name":"Department of Microbiology & Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA"},{"name":"World Reference Center for Emerging Viruses and Arboviruses, University of Texas Medical Branch, Galveston, TX 77555, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2450-2374","authenticated-orcid":false,"given":"Shannan L.","family":"Rossi","sequence":"additional","affiliation":[{"name":"Sealy Institute for Vaccine Sciences, University of Texas Medical Branch, Galveston, TX 77555, USA"},{"name":"Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555, USA"},{"name":"Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, TX 77555, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8016-8556","authenticated-orcid":false,"given":"Scott C.","family":"Weaver","sequence":"additional","affiliation":[{"name":"Department of Microbiology & Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA"},{"name":"Sealy Institute for Vaccine Sciences, University of Texas Medical Branch, Galveston, TX 77555, USA"},{"name":"World Reference Center for Emerging Viruses and Arboviruses, University of Texas Medical Branch, Galveston, TX 77555, USA"},{"name":"Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555, USA"},{"name":"Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, TX 77555, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tian","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Microbiology & Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA"},{"name":"Sealy Institute for Vaccine Sciences, University of Texas Medical Branch, Galveston, TX 77555, USA"},{"name":"Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555, USA"},{"name":"Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, TX 77555, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"837","DOI":"10.2217\/fmb.09.59","article-title":"A structural and functional perspective of alphavirus replication and assembly","volume":"4","author":"Jose","year":"2009","journal-title":"Future Microbiol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"8904","DOI":"10.1128\/JVI.01289-12","article-title":"Complete genome sequence of a chikungunya virus isolated in Guangdong, China","volume":"86","author":"Li","year":"2012","journal-title":"J. Virol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"46923","DOI":"10.1074\/jbc.M207847200","article-title":"Alphavirus 6K proteins form ion channels","volume":"277","author":"Melton","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e0158621","DOI":"10.1128\/jvi.01586-21","article-title":"Emerging Chikungunya Virus Variants at the E1-E1 Interglycoprotein Spike Interface Impact Virus Attachment and Inflammation","volume":"96","author":"Rangel","year":"2022","journal-title":"J. Virol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"8511","DOI":"10.1128\/JVI.00449-13","article-title":"Functional characterization of the alphavirus TF protein","volume":"87","author":"Snyder","year":"2013","journal-title":"J. Virol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/j.antiviral.2015.04.016","article-title":"Chikungunya: Evolutionary history and recent epidemic spread","volume":"120","author":"Weaver","year":"2015","journal-title":"Antivir. Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/0035-9203(55)90080-8","article-title":"An epidemic of virus disease in Southern Province, Tanganyika Territory, in 1952-53. I. Clinical features","volume":"49","author":"Robinson","year":"1955","journal-title":"Trans. R. Soc. Trop. Med. Hyg."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1038\/nm.2105","article-title":"A virus-like particle vaccine for epidemic Chikungunya virus protects nonhuman primates against infection","volume":"16","author":"Akahata","year":"2010","journal-title":"Nat. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1016\/S1473-3099(15)70043-5","article-title":"Immunogenicity, safety, and tolerability of a recombinant measles-virus-based chikungunya vaccine: A randomised, double-blind, placebo-controlled, active-comparator, first-in-man trial","volume":"15","author":"Ramsauer","year":"2015","journal-title":"Lancet Infect. Dis."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"taad156","DOI":"10.1093\/jtm\/taad156","article-title":"A randomized, double-blinded Phase 3 study to demonstrate lot-to-lot consistency and to confirm immunogenicity and safety of the live-attenuated chikungunya virus vaccine candidate VLA1553 in healthy adultsdagger","volume":"31","author":"McMahon","year":"2024","journal-title":"J. Travel Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"6084","DOI":"10.1128\/JVI.06449-11","article-title":"Attenuation of Chikungunya virus vaccine strain 181\/clone 25 is determined by two amino acid substitutions in the E2 envelope glycoprotein","volume":"86","author":"Gorchakov","year":"2012","journal-title":"J. Virol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"3353","DOI":"10.1016\/j.vaccine.2013.05.059","article-title":"Deciphering the protective role of adaptive immunity to CHIKV\/IRES a novel candidate vaccine against Chikungunya in the A129 mouse model","volume":"31","author":"Chu","year":"2013","journal-title":"Vaccine"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1128\/JVI.01860-12","article-title":"A chimeric vesiculo\/alphavirus is an effective alphavirus vaccine","volume":"87","author":"Chattopadhyay","year":"2013","journal-title":"J. Virol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"5030","DOI":"10.1016\/j.vaccine.2008.07.054","article-title":"Chimeric alphavirus vaccine candidates for chikungunya","volume":"26","author":"Wang","year":"2008","journal-title":"Vaccine"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"643","DOI":"10.4049\/jimmunol.107.3.643","article-title":"Production and evaluation of a formalin-killed Chikungunya vaccine","volume":"107","author":"Harrison","year":"1971","journal-title":"J. Immunol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.crimmu.2021.03.001","article-title":"Prime-boost with Chikungunya virus E2 envelope protein combined with Poly (I:C) induces specific humoral and cellular immune responses","volume":"2","author":"Amaral","year":"2021","journal-title":"Curr. Res. Immunol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"5128","DOI":"10.1016\/j.vaccine.2008.03.060","article-title":"Immunogenicity of novel consensus-based DNA vaccines against Chikungunya virus","volume":"26","author":"Muthumani","year":"2008","journal-title":"Vaccine"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1343","DOI":"10.1016\/S0140-6736(25)00345-9","article-title":"Chikungunya virus virus-like particle vaccine safety and immunogenicity in adolescents and adults in the USA: A phase 3, randomised, double-blind, placebo-controlled trial","volume":"405","author":"Richardson","year":"2025","journal-title":"Lancet"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"14622","DOI":"10.1073\/pnas.1204787109","article-title":"Eilat virus, a unique alphavirus with host range restricted to insects by RNA replication","volume":"109","author":"Nasar","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1404","DOI":"10.1128\/JVI.01856-14","article-title":"Eilat virus host range restriction is present at multiple levels of the virus life cycle","volume":"89","author":"Nasar","year":"2015","journal-title":"J. Virol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1038\/nm.4253","article-title":"A chikungunya fever vaccine utilizing an insect-specific virus platform","volume":"23","author":"Erasmus","year":"2017","journal-title":"Nat. Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1038\/s41541-024-01047-z","article-title":"A safe insect-based chikungunya fever vaccine affords rapid and durable protection in cynomolgus macaques","volume":"9","author":"Adam","year":"2024","journal-title":"NPJ Vaccines"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1128\/JVI.02159-15","article-title":"gammadelta T Cells Play a Protective Role in Chikungunya Virus-Induced Disease","volume":"90","author":"Long","year":"2016","journal-title":"J. Virol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1080\/22221751.2021.1886598","article-title":"Optimized production and immunogenicity of an insect virus-based chikungunya virus candidate vaccine in cell culture and animal models","volume":"10","author":"Adam","year":"2021","journal-title":"Emerg. Microbes Infect."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"3804","DOI":"10.4049\/jimmunol.1800892","article-title":"Multiplexed FluoroSpot for the Analysis of Dengue Virus- and Zika Virus-Specific and Cross-Reactive Memory B Cells","volume":"201","author":"Adam","year":"2018","journal-title":"J. Immunol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"106059","DOI":"10.1016\/j.antiviral.2024.106059","article-title":"Pellino-1, a therapeutic target for control of SARS-CoV-2 infection and disease severity","volume":"233","author":"Wang","year":"2025","journal-title":"Antivir. Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1590\/0037-8682-0403-2016","article-title":"Sensitivity and detection of chikungunya viral genetic material using several PCR-based approaches","volume":"50","author":"Esposito","year":"2017","journal-title":"Rev. Soc. Bras. Med. Trop."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/j.jsbmb.2009.01.019","article-title":"Influence of testosterone and a novel SARM on gene expression in whole blood of Macaca fascicularis","volume":"114","author":"Riedmaier","year":"2009","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1111\/j.1574-695X.2011.00840.x","article-title":"Vgamma4+ T cells regulate host immune response to West Nile virus infection","volume":"63","author":"Welte","year":"2011","journal-title":"FEMS Immunol. Med. Microbiol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"e02097-16","DOI":"10.1128\/JVI.02097-16","article-title":"MAVS Is Essential for Primary CD4+ T Cell Immunity but Not for Recall T Cell Responses following an Attenuated West Nile Virus Infection","volume":"91","author":"Luo","year":"2017","journal-title":"J. Virol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1825","DOI":"10.4049\/jimmunol.177.3.1825","article-title":"Gamma delta T cells facilitate adaptive immunity against West Nile virus infection in mice","volume":"177","author":"Wang","year":"2006","journal-title":"J. Immunol."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Broeckel, R.M., Haese, N., Ando, T., Dmitriev, I., Kreklywich, C.N., Powers, J., Denton, M., Smith, P., Morrison, T.E., and Heise, M. (2019). Vaccine-Induced Skewing of T Cell Responses Protects Against Chikungunya Virus Disease. Front. Immunol., 10.","DOI":"10.3389\/fimmu.2019.02563"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"e02036-19","DOI":"10.1128\/JVI.02036-19","article-title":"Chikungunya Virus Evades Antiviral CD8+ T Cell Responses To Establish Persistent Infection in Joint-Associated Tissues","volume":"94","author":"Davenport","year":"2020","journal-title":"J. Virol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"7893","DOI":"10.1128\/JVI.00998-15","article-title":"Expanding regulatory T cells alleviates chikungunya virus-induced pathology in mice","volume":"89","author":"Lee","year":"2015","journal-title":"J. Virol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1326","DOI":"10.1016\/j.celrep.2016.06.076","article-title":"Pathogenic Chikungunya Virus Evades B Cell Responses to Establish Persistence","volume":"16","author":"Hawman","year":"2016","journal-title":"Cell Rep."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Seymour, R.L., Adams, A.P., Leal, G., Alcorn, M.D., and Weaver, S.C. (2015). A Rodent Model of Chikungunya Virus Infection in RAG1 -\/- Mice, with Features of Persistence, for Vaccine Safety Evaluation. PLoS Negl. Trop. Dis., 9.","DOI":"10.1371\/journal.pntd.0003800"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1007\/s002810000047","article-title":"Intraepithelial gamma delta T lymphocytes: Sentinel cells at mucosal barriers","volume":"22","author":"Ferrick","year":"2000","journal-title":"Springer Semin. Immunopathol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"662","DOI":"10.1002\/eji.200839120","article-title":"IL-17-producing gammadelta T cells","volume":"39","author":"Roark","year":"2009","journal-title":"Eur. J. Immunol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"5656","DOI":"10.4049\/jimmunol.175.9.5656","article-title":"Lyme arthritis synovial gammadelta T cells instruct dendritic cells via fas ligand","volume":"175","author":"Collins","year":"2005","journal-title":"J. Immunol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1006\/clim.2002.5218","article-title":"Human gamma delta T cells induce dendritic cell maturation","volume":"103","author":"Ismaili","year":"2002","journal-title":"Clin. Immunol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1575","DOI":"10.1084\/jem.20021515","article-title":"CD1-mediated gamma\/delta T cell maturation of dendritic cells","volume":"196","author":"Leslie","year":"2002","journal-title":"J. Exp. Med."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1084\/jem.20050810","article-title":"Dendritic cell maturation by innate lymphocytes: Coordinated stimulation of innate and adaptive immunity","volume":"202","author":"Munz","year":"2005","journal-title":"J. Exp. Med."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"e01274-17","DOI":"10.1128\/JVI.01274-17","article-title":"Novel Insect-Specific Eilat Virus-Based Chimeric Vaccine Candidates Provide Durable, Mono- and Multivalent, Single-Dose Protection against Lethal Alphavirus Challenge","volume":"92","author":"Erasmus","year":"2018","journal-title":"J. Virol."}],"container-title":["Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-0817\/14\/9\/863\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:36:11Z","timestamp":1760034971000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-0817\/14\/9\/863"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,30]]},"references-count":43,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2025,9]]}},"alternative-id":["pathogens14090863"],"URL":"https:\/\/doi.org\/10.3390\/pathogens14090863","relation":{},"ISSN":["2076-0817"],"issn-type":[{"type":"electronic","value":"2076-0817"}],"subject":[],"published":{"date-parts":[[2025,8,30]]}}}