{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T20:39:19Z","timestamp":1772138359226,"version":"3.50.1"},"reference-count":22,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2022,2,23]],"date-time":"2022-02-23T00:00:00Z","timestamp":1645574400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Disease","doi-asserted-by":"publisher","award":["T32 AI049820"],"award-info":[{"award-number":["T32 AI049820"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Disease","doi-asserted-by":"publisher","award":["T32 AI060525"],"award-info":[{"award-number":["T32 AI060525"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Disease","doi-asserted-by":"publisher","award":["F31 AI147440"],"award-info":[{"award-number":["F31 AI147440"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Disease","doi-asserted-by":"publisher","award":["R01 AI123348"],"award-info":[{"award-number":["R01 AI123348"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"name":"UPMC Children\u2019s Hospital of Pittsburgh"},{"DOI":"10.13039\/100000934","name":"Heinz Endowments","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000934","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,2,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Chikungunya virus (CHIKV) is an arbovirus that periodically emerges to cause large epidemics of arthritic disease. Although the robust immunity elicited by live-attenuated virus (LAV) vaccine candidates makes them attractive, CHIKV vaccine development has been hampered by a high threshold for acceptable adverse events.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We evaluated the vaccine potential of a recently described LAV, skeletal muscle-restricted virus (SKE), that exhibits diminished replication in skeletal muscle due to insertion of target sequences for skeletal muscle-specific miR-206. We also evaluated whether these target sequences could augment safety of an LAV encoding a known attenuating mutation, E2 G82R. Attenuation of viruses containing these mutations was compared with a double mutant, SKE G82R.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>SKE was attenuated in both immunodeficient and immunocompetent mice and induced a robust neutralizing antibody response, indicating its vaccine potential. However, only SKE G82R elicited diminished swelling in immunocompetent mice at early time points postinoculation, indicating that these mutations synergistically enhance safety of the vaccine candidate.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These data suggest that restriction of LAV replication in skeletal muscle enhances tolerability of reactogenic vaccine candidates and may improve the rational design of CHIKV vaccines.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/infdis\/jiac066","type":"journal-article","created":{"date-parts":[[2022,2,22]],"date-time":"2022-02-22T15:14:43Z","timestamp":1645542883000},"page":"457-465","source":"Crossref","is-referenced-by-count":5,"title":["Chikungunya Virus Vaccine Candidate Incorporating Synergistic Mutations Is Attenuated and Protects Against Virulent Virus Challenge"],"prefix":"10.1093","volume":"227","author":[{"given":"Anthony J","family":"Lentscher","sequence":"first","affiliation":[{"name":"Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine , Pittsburgh, Pennsylvania , USA"},{"name":"Institute for Infection, Inflammation, and Immunity, UPMC Children\u2019s Hospital of Pittsburgh , Pittsburgh, Pennsylvania , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicole","family":"McAllister","sequence":"additional","affiliation":[{"name":"Department of Biology, Seton Hill University , Greenburg, Pennsylvania , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kira A","family":"Griswold","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine , Pittsburgh, Pennsylvania , USA"},{"name":"Institute for Infection, Inflammation, and Immunity, UPMC Children\u2019s Hospital of Pittsburgh , Pittsburgh, Pennsylvania , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James L","family":"Martin","sequence":"additional","affiliation":[{"name":"Institute for Infection, Inflammation, and Immunity, UPMC Children\u2019s Hospital of Pittsburgh , Pittsburgh, Pennsylvania , USA"},{"name":"Department of Pediatrics, University of Pittsburgh School of Medicine , Pittsburgh, Pennsylvania , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Olivia L","family":"Welsh","sequence":"additional","affiliation":[{"name":"Institute for Infection, Inflammation, and Immunity, UPMC Children\u2019s Hospital of Pittsburgh , Pittsburgh, Pennsylvania , USA"},{"name":"Department of Pediatrics, University of Pittsburgh School of Medicine , Pittsburgh, Pennsylvania , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Danica M","family":"Sutherland","sequence":"additional","affiliation":[{"name":"Institute for Infection, Inflammation, and Immunity, UPMC Children\u2019s Hospital of Pittsburgh , Pittsburgh, Pennsylvania , USA"},{"name":"Department of Pediatrics, University of Pittsburgh School of Medicine , Pittsburgh, Pennsylvania , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laurie A","family":"Silva","sequence":"additional","affiliation":[{"name":"Institute for Infection, Inflammation, and Immunity, UPMC Children\u2019s Hospital of Pittsburgh , Pittsburgh, Pennsylvania , USA"},{"name":"Department of Pediatrics, University of Pittsburgh School of Medicine , Pittsburgh, Pennsylvania , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1853-8741","authenticated-orcid":false,"given":"Terence S","family":"Dermody","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine , Pittsburgh, Pennsylvania , USA"},{"name":"Institute for Infection, Inflammation, and Immunity, UPMC Children\u2019s Hospital of Pittsburgh , Pittsburgh, Pennsylvania , USA"},{"name":"Department of Pediatrics, University of Pittsburgh School of Medicine , Pittsburgh, Pennsylvania , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2022,2,23]]},"reference":[{"key":"2023053118482566900_CIT0001","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1038\/nbt.1635","article-title":"Rationalizing the development of live attenuated virus vaccines.","volume":"28","author":"Lauring","year":"2010","journal-title":"Nat Biotechnol"},{"key":"2023053118482566900_CIT0002","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1016\/j.antiviral.2013.06.009","article-title":"Chikungunya fever: epidemiology, clinical syndrome, pathogenesis and therapy.","volume":"99","author":"Thiberville","year":"2013","journal-title":"Antiviral Res"},{"key":"2023053118482566900_CIT0003","doi-asserted-by":"crossref","first-page":"912","DOI":"10.1590\/S0074-02762011000800003","article-title":"Chikungunya virus outbreak in Kerala, India, 2007: a seroprevalence survey.","volume":"106","author":"Kumar","year":"2011","journal-title":"Mem Inst Oswaldo Cruz"},{"key":"2023053118482566900_CIT0004","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1086\/590003","article-title":"Persistent arthralgia associated with chikungunya virus: a study of 88 adult patients on reunion Island.","volume":"47","author":"Borgherini","year":"2008","journal-title":"Clin Infect Dis"},{"key":"2023053118482566900_CIT0005","doi-asserted-by":"crossref","first-page":"e1197","DOI":"10.1371\/journal.pntd.0001197","article-title":"The chikungunya epidemic on La Reunion Island in 2005-2006: a cost-of-illness study.","volume":"5","author":"Soumahoro","year":"2011","journal-title":"PLoS NeglTrop Dis"},{"key":"2023053118482566900_CIT0006","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/0264-410X(86)90003-4","article-title":"Development of an attenuated strain of chikungunya virus for use in vaccine production.","volume":"4","author":"Levitt","year":"1986","journal-title":"Vaccine"},{"key":"2023053118482566900_CIT0007","doi-asserted-by":"crossref","first-page":"681","DOI":"10.4269\/ajtmh.2000.62.681","article-title":"Phase II safety and immunogenicity study of live chikungunya virus vaccine TSI-GSD-218.","volume":"62","author":"Edelman","year":"2000","journal-title":"Am J Trop Med Hyg"},{"key":"2023053118482566900_CIT0008","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":"2023053118482566900_CIT0009","doi-asserted-by":"crossref","first-page":"2385","DOI":"10.1128\/JVI.03116-13","article-title":"A single-amino-acid polymorphism in chikungunya virus E2 glycoprotein influences glycosaminoglycan utilization.","volume":"88","author":"Silva","year":"2013","journal-title":"J Virol"},{"key":"2023053118482566900_CIT0010","doi-asserted-by":"crossref","first-page":"12180","DOI":"10.1128\/JVI.01672-14","article-title":"Residue 82 of the Chikungunya virus E2 attachment protein modulates viral dissemination and arthritis in mice.","volume":"88","author":"Ashbrook","year":"2014","journal-title":"J Virol"},{"key":"2023053118482566900_CIT0011","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":"2023053118482566900_CIT0012","author":"Glass"},{"key":"2023053118482566900_CIT0013","doi-asserted-by":"crossref","first-page":"1466","DOI":"10.1172\/JCI129893","article-title":"Chikungunya virus replication in skeletal muscle cells is required for disease development.","volume":"130","author":"Lentscher","year":"2020","journal-title":"J Clin Invest"},{"key":"2023053118482566900_CIT0014","doi-asserted-by":"crossref","first-page":"e00693","DOI":"10.1128\/mBio.00693-16","article-title":"Antagonism of the sodium-potassium ATPase impairs chikungunya virus infection.","volume":"7","author":"Ashbrook","year":"2016","journal-title":"mBio"},{"key":"2023053118482566900_CIT0015","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/j.ajpath.2010.11.018","article-title":"A mouse model of chikungunya virus-induced musculoskeletal inflammatory disease: evidence of arthritis, tenosyovitis, myositis, and persistence.","volume":"178","author":"Morrison","year":"2011","journal-title":"Am J Pathol"},{"key":"2023053118482566900_CIT0016","doi-asserted-by":"crossref","first-page":"6295","DOI":"10.4049\/jimmunol.1300304","article-title":"An essential role of antibodies in the control of chikungunya virus infection.","volume":"190","author":"Lum","year":"2013","journal-title":"J Immunol"},{"key":"2023053118482566900_CIT0017","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/j.chom.2015.06.009","article-title":"Isolation and characterization of broad and ultrapotent human monoclonal antibodies with therapeutic activity against chikungunya virus.","volume":"18","author":"Smith","year":"2015","journal-title":"Cell Host Microbe"},{"key":"2023053118482566900_CIT0018","doi-asserted-by":"crossref","first-page":"e0006693","DOI":"10.1371\/journal.pntd.0006693","article-title":"An attenuated replication-competent chikungunya virus with a fluorescently tagged envelope.","volume":"12","author":"Jin","year":"2018","journal-title":"PLoS NeglTrop Dis"},{"key":"2023053118482566900_CIT0019","doi-asserted-by":"crossref","first-page":"e1002142","DOI":"10.1371\/journal.ppat.1002142","article-title":"Novel chikungunya vaccine candidate with an IRES-based attenuation and host range alteration mechanism.","volume":"7","author":"Plante","year":"2011","journal-title":"PLoS Pathog"},{"key":"2023053118482566900_CIT0020","doi-asserted-by":"crossref","first-page":"2858","DOI":"10.1128\/JVI.03453-13","article-title":"Novel attenuated chikungunya vaccine candidates elicit protective immunity in C57BL\/6 mice.","volume":"88","author":"Hallengard","year":"2014","journal-title":"J Virol"},{"key":"2023053118482566900_CIT0021","doi-asserted-by":"crossref","first-page":"e83527","DOI":"10.1172\/jci.insight.83527","article-title":"Attenuated and vectored vaccines protect nonhuman primates against chikungunya virus.","volume":"2","author":"Roques","year":"2017","journal-title":"JCI Insight"},{"key":"2023053118482566900_CIT0022","doi-asserted-by":"crossref","first-page":"1193","DOI":"10.1016\/S1473-3099(20)30238-3","article-title":"Single-shot live-attenuated chikungunya vaccine in healthy adults: a phase 1, randomised controlled trial.","volume":"20","author":"Wressnigg","year":"2020","journal-title":"Lancet Infect Dis"}],"container-title":["The Journal of Infectious Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jid\/advance-article-pdf\/doi\/10.1093\/infdis\/jiac066\/43288628\/jiac066.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jid\/article-pdf\/227\/3\/457\/50496785\/jiac066.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jid\/article-pdf\/227\/3\/457\/50496785\/jiac066.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,31]],"date-time":"2023-05-31T14:48:59Z","timestamp":1685544539000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jid\/article\/227\/3\/457\/6535121"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,2,23]]},"references-count":22,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2022,2,23]]},"published-print":{"date-parts":[[2023,2,1]]}},"URL":"https:\/\/doi.org\/10.1093\/infdis\/jiac066","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2021.10.19.464869","asserted-by":"object"}]},"ISSN":["0022-1899","1537-6613"],"issn-type":[{"value":"0022-1899","type":"print"},{"value":"1537-6613","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2023,2,1]]},"published":{"date-parts":[[2022,2,23]]}}}