{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T03:48:39Z","timestamp":1788580119139,"version":"build-2803163510"},"update-to":[{"DOI":"10.1371\/journal.pntd.0014610","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T00:00:00Z","timestamp":1787616000000}}],"reference-count":36,"publisher":"Public Library of Science (PLoS)","issue":"8","license":[{"start":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T00:00:00Z","timestamp":1785715200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100032488","name":"Emergent BioSolutions Inc","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100032488","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100018937","name":"Bavarian Nordic","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100018937","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100016820","name":"Vaccine Research Center","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100016820","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosntds.org"],"crossmark-restriction":false},"short-container-title":["PLoS Negl Trop Dis"],"abstract":"<jats:p>\n                    Chikungunya virus (CHIKV) neutralization assays, which measure virus-neutralizing activity, play a pivotal role in evaluating vaccine effectiveness and monitoring immunity. As CHIKV continues to spread beyond endemic tropical regions, causing more frequent outbreaks and debilitating disease, it remains a serious global health concern. Vaccination can help alleviate these burdens by inducing neutralizing antibodies, which are also produced following natural infection. Neutralizing antibodies can prevent virus infection and are considered a key correlate of protection against disease caused by CHIKV. Accurate assessment of neutralizing antibodies is therefore essential for both vaccine evaluation and public health surveillance. This work introduces a validated luciferase-based high-throughput CHIKV neutralization assay (CHIKV-luc NT\n                    <jats:sub>80<\/jats:sub>\n                    ) for quantifying serum neutralizing antibodies. The assay uses a genetically engineered reporter virus (CHIKV181\/25-luc) that expresses luciferase, allowing\n                    <jats:italic>in vitro<\/jats:italic>\n                    viral infectivity to be measured using luminescence rather than manual plaque counting. Compared to the traditional plaque reduction neutralization test (PRNT), this method is faster, easier, more reproducible, and better suited for large-scale clinical studies associated with a high biological sample burden, due to its scalability. The use of a stringent 80% neutralization titer threshold (NT\n                    <jats:sub>80<\/jats:sub>\n                    ) also provides a more stringent measure of antibodies compared to conventional NT\n                    <jats:sub>50<\/jats:sub>\n                    values. The assay was compared to other methods, having high concordance (r\u2009\u2248\u20090.9) and low bias (\u226415%), supporting its analytical reliability, qualified for phase 2 clinical trials, and validated for phase 3 clinical sample testing. The assay contributed to the establishment of the first World Health Organization International Standard for anti-CHIKV (code number 1502\/19), and its results harmonized well with other virus neutralization methods. Neutralization titer results from preclinical and clinical serum sample testing supported the characterization of a surrogate threshold of protection, and licensure of VIMKUNYA (CHIKV virus-like particle [VLP] vaccine).\n                  <\/jats:p>","DOI":"10.1371\/journal.pntd.0014610","type":"journal-article","created":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T17:38:50Z","timestamp":1785778730000},"page":"e0014610","update-policy":"https:\/\/doi.org\/10.1371\/journal.pntd.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["Luciferase unleashed: Lighting the path to vaccine approval using a novel high-throughput chikungunya virus neutralization assay"],"prefix":"10.1371","volume":"20","author":[{"given":"Jason","family":"Mendy","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa","family":"Bedell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7751-1042","authenticated-orcid":true,"given":"Lauren C.","family":"Tindale","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason S.","family":"Richardson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Na","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yari","family":"Fontebasso","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theodore C.","family":"Pierson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keith","family":"Gottlieb","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lo","family":"Vang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,8,3]]},"reference":[{"issue":"4","key":"pntd.0014610.ref001","doi-asserted-by":"crossref","DOI":"10.1093\/jtm\/taad062","article-title":"Climate change and vector-borne diseases: a multi-omics approach of temperature-induced changes in the mosquito","volume":"30","author":"R Bellone","year":"2023","journal-title":"J Travel Med"},{"key":"pntd.0014610.ref002","doi-asserted-by":"crossref","first-page":"1488106","DOI":"10.3389\/fmicb.2024.1488106","article-title":"Innovative strategies and challenges mosquito-borne disease control amidst climate change","volume":"15","author":"Y Zhang","year":"2024","journal-title":"Front Microbiol"},{"issue":"3","key":"pntd.0014610.ref003","doi-asserted-by":"crossref","DOI":"10.1371\/annotation\/850ee20f-2641-46ac-b0c6-ef4ae79b6de6","article-title":"Chikungunya virus-associated long-term arthralgia: a 36-month prospective longitudinal study","volume":"7","author":"C Schilte","year":"2013","journal-title":"PLoS Negl Trop Dis"},{"issue":"3","key":"pntd.0014610.ref004","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pntd.0009055","article-title":"Measuring the global burden of chikungunya and Zika viruses: a systematic review","volume":"15","author":"CJ Puntasecca","year":"2021","journal-title":"PLoS Negl Trop Dis"},{"issue":"6","key":"pntd.0014610.ref005","doi-asserted-by":"crossref","first-page":"301","DOI":"10.3390\/tropicalmed8060301","article-title":"Epidemiology and economic burden of Chikungunya: a systematic literature review","volume":"8","author":"LB Costa","year":"2023","journal-title":"Trop Med Infect Dis"},{"issue":"9","key":"pntd.0014610.ref006","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1111\/tmi.70012","article-title":"Burden of chikungunya fever and its economic and social impacts worldwide: a systematic review","volume":"30","author":"VD Ped\u00ed","year":"2025","journal-title":"Trop Med Int Health"},{"issue":"1","key":"pntd.0014610.ref007","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/j.virol.2007.09.028","article-title":"Production and characterization of mouse monoclonal antibodies reactive to Chikungunya envelope E2 glycoprotein","volume":"371","author":"A-C Br\u00e9hin","year":"2008","journal-title":"Virology"},{"issue":"7","key":"pntd.0014610.ref008","doi-asserted-by":"crossref","first-page":"1147","DOI":"10.1093\/infdis\/jis033","article-title":"Early appearance of neutralizing immunoglobulin G3 antibodies is associated with chikungunya virus clearance and long-term clinical protection","volume":"205","author":"Y-W Kam","year":"2012","journal-title":"J Infect Dis"},{"issue":"5","key":"pntd.0014610.ref009","article-title":"High rate of subclinical chikungunya virus infection and association of neutralizing antibody with protection in a prospective cohort in the Philippines","volume":"9","author":"I-K Yoon","year":"2015","journal-title":"PLoS Negl Trop Dis"},{"issue":"1","key":"pntd.0014610.ref010","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1007\/s12275-020-9384-0","article-title":"Development of a neutralization assay based on the pseudotyped chikungunya virus of a Korean isolate","volume":"58","author":"W-C Chung","year":"2020","journal-title":"J Microbiol"},{"key":"pntd.0014610.ref011","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1186\/1743-422X-10-235","article-title":"Virus replicon particle based Chikungunya virus neutralization assay using Gaussia luciferase as readout","volume":"10","author":"S Gl\u00e4sker","year":"2013","journal-title":"Virol J"},{"issue":"1","key":"pntd.0014610.ref012","doi-asserted-by":"crossref","first-page":"1076","DOI":"10.1186\/s12879-024-09973-y","article-title":"Facile quantitative diagnostic testing for neutralizing antibodies against Chikungunya virus","volume":"24","author":"H-C Lin","year":"2024","journal-title":"BMC Infect Dis"},{"issue":"10394","key":"pntd.0014610.ref013","doi-asserted-by":"crossref","first-page":"2138","DOI":"10.1016\/S0140-6736(23)00641-4","article-title":"Safety and immunogenicity of a single-shot live-attenuated chikungunya vaccine: a double-blind, multicentre, randomised, placebo-controlled, phase 3 trial","volume":"401","author":"M Schneider","year":"2023","journal-title":"Lancet"},{"issue":"6","key":"pntd.0014610.ref014","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1007\/s40259-024-00677-y","article-title":"Chikungunya virus vaccines: a review of IXCHIQ and PXVX0317 from pre-clinical evaluation to licensure","volume":"38","author":"WC Weber","year":"2024","journal-title":"BioDrugs"},{"issue":"3","key":"pntd.0014610.ref015","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":"W Akahata","year":"2010","journal-title":"Nat Med"},{"key":"pntd.0014610.ref016","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.coviro.2016.03.001","article-title":"Engineering virus-like particles as vaccine platforms","volume":"18","author":"KM Frietze","year":"2016","journal-title":"Curr Opin Virol"},{"issue":"1","key":"pntd.0014610.ref017","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1080\/14760584.2025.2508517","article-title":"Virus-like particles: a versatile and effective vaccine platform","volume":"24","author":"MF Bachmann","year":"2025","journal-title":"Expert Rev Vaccines"},{"key":"pntd.0014610.ref018","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.smim.2017.08.014","article-title":"Major findings and recent advances in virus-like particle (VLP)-based vaccines","volume":"34","author":"MO Mohsen","year":"2017","journal-title":"Semin Immunol"},{"issue":"10487","key":"pntd.0014610.ref019","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":"JS Richardson","year":"2025","journal-title":"Lancet"},{"issue":"10487","key":"pntd.0014610.ref020","doi-asserted-by":"crossref","first-page":"1353","DOI":"10.1016\/S0140-6736(25)00372-1","article-title":"Chikungunya virus virus-like particle vaccine safety and immunogenicity in adults older than 65 years: a phase 3, randomised, double-blind, placebo-controlled trial","volume":"405","author":"LC Tindale","year":"2025","journal-title":"Lancet"},{"issue":"11","key":"pntd.0014610.ref021","doi-asserted-by":"crossref","first-page":"5046","DOI":"10.1128\/JCM.41.11.5046-5052.2003","article-title":"Quantifying adenovirus-neutralizing antibodies by luciferase transgene detection: addressing preexisting immunity to vaccine and gene therapy vectors","volume":"41","author":"MC Sprangers","year":"2003","journal-title":"J Clin Microbiol"},{"issue":"12","key":"pntd.0014610.ref022","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0082380","article-title":"Pre-clinical development of a recombinant, replication-competent adenovirus serotype 4 vector vaccine expressing HIV-1 envelope 1086 clade C","volume":"8","author":"J Alexander","year":"2013","journal-title":"PLoS One"},{"issue":"6","key":"pntd.0014610.ref023","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":"R Edelman","year":"2000","journal-title":"Am J Trop Med Hyg"},{"issue":"11","key":"pntd.0014610.ref024","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":"R Gorchakov","year":"2012","journal-title":"J Virol"},{"issue":"1","key":"pntd.0014610.ref025","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1038\/s41572-023-00429-2","article-title":"Chikungunya fever","volume":"9","author":"K Bartholomeeusen","year":"2023","journal-title":"Nat Rev Dis Primers"},{"issue":"10","key":"pntd.0014610.ref026","doi-asserted-by":"crossref","first-page":"1487","DOI":"10.1093\/infdis\/jiw431","article-title":"A virus-like particle vaccine elicits broad neutralizing antibody responses in humans to all Chikungunya virus genotypes","volume":"214","author":"L Goo","year":"2016","journal-title":"J Infect Dis"},{"issue":"1","key":"pntd.0014610.ref027","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":"SA Smith","year":"2015","journal-title":"Cell Host Microbe"},{"issue":"8","key":"pntd.0014610.ref028","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pntd.0004960","article-title":"Antigenic variation of East\/Central\/South African and Asian chikungunya virus genotypes in neutralization by immune sera","volume":"10","author":"C Chua","year":"2016","journal-title":"PLoS Negl Trop Dis"},{"key":"pntd.0014610.ref029","unstructured":"Baylis SA, Yue C, Panning M, Pauly M, Rodrigues L, Faddy H, et al. Collaborative Study to Evaluate a Candidate World Health Organization International Standard for Antibodies to Chikungunya Virus. Expert committee on biological standardization Geneva, 24 to 28 October 2022 [Internet]. 2022 [cited 2025 Nov 24] Available from: www.who.int\/publications\/m\/item\/who-bs-2022.2434"},{"issue":"9959","key":"pntd.0014610.ref030","doi-asserted-by":"crossref","first-page":"2046","DOI":"10.1016\/S0140-6736(14)61185-5","article-title":"Safety and tolerability of chikungunya virus-like particle vaccine in healthy adults: a phase 1 dose-escalation trial","volume":"384","author":"L-J Chang","year":"2014","journal-title":"Lancet"},{"issue":"14","key":"pntd.0014610.ref031","doi-asserted-by":"crossref","first-page":"1369","DOI":"10.1001\/jama.2020.2477","article-title":"Effect of a chikungunya virus-like particle vaccine on safety and tolerability outcomes: a randomized clinical trial","volume":"323","author":"GL Chen","year":"2020","journal-title":"JAMA"},{"issue":"9","key":"pntd.0014610.ref032","doi-asserted-by":"crossref","first-page":"1343","DOI":"10.1016\/S1473-3099(22)00226-2","article-title":"Safety and immunogenicity of PXVX0317, an aluminium hydroxide-adjuvanted chikungunya virus-like particle vaccine: a randomised, double-blind, parallel-group, phase 2 trial","volume":"22","author":"SR Bennett","year":"2022","journal-title":"Lancet Infect Dis"},{"issue":"4","key":"pntd.0014610.ref033","doi-asserted-by":"crossref","first-page":"101000","DOI":"10.1016\/j.lanmic.2024.101000","article-title":"Safety and immunogenicity of an adjuvanted chikungunya virus virus-like particle (CHIKV VLP) vaccine in previous recipients of other alphavirus vaccines versus alphavirus vaccine-naive controls: an open-label, parallel-group, age-matched, sex-matched, phase 2 randomised controlled study","volume":"6","author":"MJ Hamer","year":"2025","journal-title":"Lancet Microbe"},{"issue":"6","key":"pntd.0014610.ref034","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pntd.0004773","article-title":"Seroprevalence of anti-chikungunya virus antibodies in children and adults in Managua, Nicaragua, after the first Chikungunya Epidemic, 2014-2015","volume":"10","author":"G Kuan","year":"2016","journal-title":"PLoS Negl Trop Dis"},{"key":"pntd.0014610.ref035","volume-title":"R: A language and environment for statistical computing","author":"R Core Team","year":"2017"},{"issue":"1","key":"pntd.0014610.ref036","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1038\/s41541-025-01360-1","article-title":"Passive transfer of human sera from chikungunya virus virus-like particle vaccine (Vimkunya) recipients fully protects non-human primates from viremia","volume":"11","author":"CS Morello","year":"2026","journal-title":"NPJ Vaccines"}],"updated-by":[{"DOI":"10.1371\/journal.pntd.0014610","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T00:00:00Z","timestamp":1787616000000}}],"container-title":["PLOS Neglected Tropical Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pntd.0014610","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T17:49:05Z","timestamp":1787680145000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pntd.0014610"}},"subtitle":[],"editor":[{"given":"Jonas","family":"Klingstr\u00f6m","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2026,8,3]]},"references-count":36,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2026,8,3]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pntd.0014610","relation":{},"ISSN":["1935-2735"],"issn-type":[{"value":"1935-2735","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,3]]}}}