{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T05:12:12Z","timestamp":1788930732482,"version":"build-2803163510"},"update-to":[{"DOI":"10.1371\/journal.pntd.0010588","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2022,7,18]],"date-time":"2022-07-18T00:00:00Z","timestamp":1658102400000}}],"reference-count":117,"publisher":"Public Library of Science (PLoS)","issue":"7","license":[{"start":{"date-parts":[[2022,7,6]],"date-time":"2022-07-06T00:00:00Z","timestamp":1657065600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosntds.org"],"crossmark-restriction":false},"short-container-title":["PLoS Negl Trop Dis"],"abstract":"<jats:p>Zika virus (ZIKV) is a mosquito-borne flavivirus with maternal infection associated with preterm birth, congenital malformations, and fetal death, and adult infection associated with Guillain-Barr\u00e9 syndrome. Recent widespread endemic transmission of ZIKV and the potential for future outbreaks necessitate the development of an effective vaccine. We developed a ZIKV vaccine candidate based on virus-like-particles (VLPs) generated following transfection of mammalian HEK293T cells using a plasmid encoding the pre-membrane\/membrane (prM\/M) and envelope (E) structural protein genes. VLPs were collected from cell culture supernatant and purified by column chromatography with yields of approximately 1-2mg\/L. To promote increased particle yields, a single amino acid change of phenylalanine to alanine was made in the E fusion loop at position 108 (F108A) of the lead VLP vaccine candidate. This mutation resulted in a modest 2-fold increase in F108A VLP production with no detectable prM processing by furin to a mature particle, in contrast to the lead candidate (parent). To evaluate immunogenicity and efficacy, AG129 mice were immunized with a dose titration of either the immature F108A or lead VLP (each alum adjuvanted). The resulting VLP-specific binding antibody (Ab) levels were comparable. However, geometric mean neutralizing Ab (nAb) titers using a recombinant ZIKV reporter were significantly lower with F108A immunization compared to lead. After virus challenge, all lead VLP-immunized groups showed a significant 3- to 4-Log<jats:sub>10<\/jats:sub> reduction in mean ZIKV RNAemia levels compared with control mice immunized only with alum, but the RNAemia reduction of 0.5 Log<jats:sub>10<\/jats:sub> for F108A groups was statistically similar to the control. Successful viral control by the lead VLP candidate following challenge supports further vaccine development for this candidate. Notably, nAb titer levels in the lead, but not F108A, VLP-immunized mice inversely correlated with RNAemia. Further evaluation of sera by an <jats:italic>in vitro<\/jats:italic> Ab-dependent enhancement assay demonstrated that the F108A VLP-induced immune sera had a significantly higher capacity to promote ZIKV infection in Fc\u03b3R-expressing cells. These data indicate that a single amino acid change in the fusion loop resulted in increased VLP yields but that the immature F108A particles were significantly diminished in their capacity to induce nAbs and provide protection against ZIKV challenge.<\/jats:p>","DOI":"10.1371\/journal.pntd.0010588","type":"journal-article","created":{"date-parts":[[2022,7,6]],"date-time":"2022-07-06T17:45:04Z","timestamp":1657129504000},"page":"e0010588","update-policy":"https:\/\/doi.org\/10.1371\/journal.pntd.corrections_policy","source":"Crossref","is-referenced-by-count":9,"title":["Zika virus-like particle vaccine fusion loop mutation increases production yield but fails to protect AG129 mice against Zika virus challenge"],"prefix":"10.1371","volume":"16","author":[{"given":"Danielle","family":"Thompson","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ben","family":"Guenther","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darly","family":"Manayani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason","family":"Mendy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Smith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diego A.","family":"Espinosa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Harris","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeff","family":"Alexander","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lo","family":"Vang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8113-1173","authenticated-orcid":true,"given":"Christopher S.","family":"Morello","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2022,7,6]]},"reference":[{"issue":"2","key":"pntd.0010588.ref001","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1016\/j.coviro.2012.02.011","article-title":"Degrees of maturity: the complex structure and biology of flaviviruses","volume":"2","author":"TC Pierson","year":"2012","journal-title":"Curr Opin Virol"},{"issue":"24","key":"pntd.0010588.ref002","doi-asserted-by":"crossref","first-page":"2536","DOI":"10.1056\/NEJMoa0805715","article-title":"Zika virus outbreak on Yap Island, Federated States of Micronesia","volume":"360","author":"MR Duffy","year":"2009","journal-title":"The New England journal of medicine"},{"issue":"9","key":"pntd.0010588.ref003","doi-asserted-by":"crossref","first-page":"675","DOI":"10.2471\/BLT.16.171082","article-title":"Zika: the origin and spread of a mosquito-borne virus","volume":"94","author":"MK Kindhauser","year":"2016","journal-title":"Bull World Health Organ"},{"issue":"8","key":"pntd.0010588.ref004","doi-asserted-by":"crossref","first-page":"1232","DOI":"10.3201\/eid1408.080287","article-title":"Genetic and serologic properties of Zika virus associated with an epidemic, Yap State, Micronesia, 2007","volume":"14","author":"RS Lanciotti","year":"2008","journal-title":"Emerg Infect Dis"},{"issue":"10027","key":"pntd.0010588.ref005","doi-asserted-by":"crossref","first-page":"1531","DOI":"10.1016\/S0140-6736(16)00562-6","article-title":"Guillain-Barr\u00e9 Syndrome outbreak associated with Zika virus infection in French Polynesia: a case-control study","volume":"387","author":"VM Cao-Lormeau","year":"2016","journal-title":"Lancet"},{"issue":"9","key":"pntd.0010588.ref006","doi-asserted-by":"crossref","DOI":"10.2807\/1560-7917.ES2014.19.9.20720","article-title":"Zika virus infection complicated by Guillain-Barre syndrome\u2014case report, French Polynesia, December 2013","volume":"19","author":"E Oehler","year":"2014","journal-title":"Euro Surveill"},{"issue":"3","key":"pntd.0010588.ref007","doi-asserted-by":"crossref","first-page":"e1002755","DOI":"10.1371\/journal.pmed.1002755","article-title":"The association between Zika virus infection and microcephaly in Brazil 2015\u20132017: An observational analysis of over 4 million births","volume":"16","author":"OJ Brady","year":"2019","journal-title":"PLoS Med"},{"key":"pntd.0010588.ref008","doi-asserted-by":"crossref","first-page":"1433","DOI":"10.12688\/f1000research.19918.1","article-title":"Zika virus infection as a cause of congenital brain abnormalities and Guillain-Barr\u00e9 syndrome: A living systematic review","volume":"8","author":"MJ Counotte","year":"2019","journal-title":"F1000Res"},{"key":"pntd.0010588.ref009","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.pediatrneurol.2018.03.001","article-title":"Review: Evidence of Neurological Sequelae in Children With Acquired Zika Virus Infection","volume":"85","author":"JF Lebov","year":"2018","journal-title":"Pediatr Neurol"},{"issue":"10","key":"pntd.0010588.ref010","doi-asserted-by":"crossref","first-page":"1302","DOI":"10.1093\/cid\/cix166","article-title":"Lessons Learned at the Epicenter of Brazil\u2019s Congenital Zika Epidemic: Evidence From 87 Confirmed Cases","volume":"64","author":"JDA Meneses","year":"2017","journal-title":"Clin Infect Dis"},{"issue":"4","key":"pntd.0010588.ref011","doi-asserted-by":"crossref","DOI":"10.1128\/mSphere.00278-18","article-title":"Exhaustive TORCH Pathogen Diagnostics Corroborate Zika Virus Etiology of Congenital Malformations in Northeastern Brazil","volume":"3","author":"A Moreira-Soto","year":"2018","journal-title":"mSphere"},{"issue":"6","key":"pntd.0010588.ref012","doi-asserted-by":"crossref","DOI":"10.1128\/mBio.01390-17","article-title":"High Zika Virus Seroprevalence in Salvador, Northeastern Brazil Limits the Potential for Further Outbreaks","volume":"8","author":"EM Netto","year":"2017","journal-title":"mBio"},{"issue":"20","key":"pntd.0010588.ref013","doi-asserted-by":"crossref","first-page":"1981","DOI":"10.1056\/NEJMsr1604338","article-title":"Zika Virus and Birth Defects\u2014Reviewing the Evidence for Causality","volume":"374","author":"SA Rasmussen","year":"2016","journal-title":"The New England journal of medicine"},{"issue":"10","key":"pntd.0010588.ref014","doi-asserted-by":"crossref","first-page":"2302","DOI":"10.1084\/jem.20191061","article-title":"Risk of Zika microcephaly correlates with features of maternal antibodies","volume":"216","author":"DF Robbiani","year":"2019","journal-title":"The Journal of experimental medicine"},{"issue":"5","key":"pntd.0010588.ref015","doi-asserted-by":"crossref","first-page":"e1985","DOI":"10.1002\/rmv.1985","article-title":"Congenital Zika syndrome: Pitfalls in the placental barrier","volume":"28","author":"N Robinson","year":"2018","journal-title":"Rev Med Virol"},{"key":"pntd.0010588.ref016","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/S0065-3527(03)59002-9","article-title":"Molecular biology of flaviviruses","volume":"59","author":"BD Lindenbach","year":"2003","journal-title":"Advances in virus research"},{"issue":"7603","key":"pntd.0010588.ref017","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1038\/nature17994","article-title":"Structure of the thermally stable Zika virus","volume":"533","author":"VA Kostyuchenko","year":"2016","journal-title":"Nature"},{"issue":"2","key":"pntd.0010588.ref018","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1038\/nsmb.3352","article-title":"Structure of the immature Zika virus at 9 A resolution","volume":"24","author":"VM Prasad","year":"2017","journal-title":"Nature structural & molecular biology"},{"issue":"suppl_10","key":"pntd.0010588.ref019","doi-asserted-by":"crossref","first-page":"S935","DOI":"10.1093\/infdis\/jix515","article-title":"Zika Virus Structure, Maturation, and Receptors","volume":"216","author":"D Sirohi","year":"2017","journal-title":"The Journal of infectious diseases"},{"issue":"20","key":"pntd.0010588.ref020","doi-asserted-by":"crossref","first-page":"3269","DOI":"10.1038\/emboj.2009.245","article-title":"Structural basis for the preferential recognition of immature flaviviruses by a fusion-loop antibody","volume":"28","author":"MV Cherrier","year":"2009","journal-title":"The EMBO journal"},{"issue":"16","key":"pntd.0010588.ref021","doi-asserted-by":"crossref","first-page":"8353","DOI":"10.1128\/JVI.00696-10","article-title":"Influence of pr-M cleavage on the heterogeneity of extracellular dengue virus particles","volume":"84","author":"J Junjhon","year":"2010","journal-title":"Journal of virology"},{"issue":"5","key":"pntd.0010588.ref022","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1016\/j.tim.2011.02.002","article-title":"Partial maturation: an immune-evasion strategy of dengue virus?","volume":"19","author":"IA Rodenhuis-Zybert","year":"2011","journal-title":"Trends in microbiology"},{"issue":"10","key":"pntd.0010588.ref023","doi-asserted-by":"crossref","first-page":"2328","DOI":"10.1080\/21645515.2019.1643676","article-title":"Does structurally-mature dengue virion matter in vaccine preparation in post-Dengvaxia era?","volume":"15","author":"JU Galula","year":"2019","journal-title":"Human vaccines & immunotherapeutics"},{"issue":"547","key":"pntd.0010588.ref024","doi-asserted-by":"crossref","DOI":"10.1126\/scitranslmed.aaw9066","article-title":"Distinct neutralizing antibody correlates of protection among related Zika virus vaccines identify a role for antibody quality","volume":"12","author":"S Maciejewski","year":"2020","journal-title":"Science translational medicine"},{"key":"pntd.0010588.ref025","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1038\/s41541-018-0061-9","article-title":"Current status of Zika vaccine development: Zika vaccines advance into clinical evaluation","volume":"3","author":"ADT Barrett","year":"2018","journal-title":"NPJ Vaccines"},{"key":"pntd.0010588.ref026","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1146\/annurev-med-040717-051127","article-title":"Zika Virus Vaccine Development: Progress in the Face of New Challenges","volume":"70","author":"MS Diamond","year":"2019","journal-title":"Annual review of medicine"},{"issue":"10120","key":"pntd.0010588.ref027","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1016\/S0140-6736(17)33105-7","article-title":"Safety, tolerability, and immunogenicity of two Zika virus DNA vaccine candidates in healthy adults: randomised, open-label, phase 1 clinical trials","volume":"391","author":"MR Gaudinski","year":"2018","journal-title":"The Lancet"},{"issue":"3","key":"pntd.0010588.ref028","doi-asserted-by":"crossref","DOI":"10.3390\/tropicalmed4030104","article-title":"Zika Vaccine Development-Current Progress and Challenges for the Future","volume":"4","author":"JN Maslow","year":"2019","journal-title":"Tropical medicine and infectious disease"},{"issue":"10120","key":"pntd.0010588.ref029","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1016\/S0140-6736(17)33106-9","article-title":"Preliminary aggregate safety and immunogenicity results from three trials of a purified inactivated Zika virus vaccine candidate: phase 1, randomised, double-blind, placebo-controlled clinical trials","volume":"391","author":"K Modjarrad","year":"2018","journal-title":"Lancet"},{"issue":"2","key":"pntd.0010588.ref030","doi-asserted-by":"crossref","DOI":"10.3390\/vaccines8020266","article-title":"Current Status of Zika Virus Vaccines: Successes and Challenges","volume":"8","author":"A Pattnaik","year":"2020","journal-title":"Vaccines"},{"issue":"12","key":"pntd.0010588.ref031","doi-asserted-by":"crossref","first-page":"2572","DOI":"10.1016\/j.mayocp.2019.05.016","article-title":"Zika Vaccine Development: Current Status","volume":"94","author":"GA Poland","year":"2019","journal-title":"Mayo Clinic proceedings"},{"key":"pntd.0010588.ref032","doi-asserted-by":"crossref","first-page":"592","DOI":"10.3389\/fimmu.2020.00592","article-title":"Current Efforts in the Development of Vaccines for the Prevention of Zika and Chikungunya Virus Infections","volume":"11","author":"S Schrauf","year":"2020","journal-title":"Frontiers in immunology"},{"issue":"1","key":"pntd.0010588.ref033","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1016\/j.chom.2018.05.021","article-title":"Zika Virus Vaccine: Progress and Challenges","volume":"24","author":"C Shan","year":"2018","journal-title":"Cell Host Microbe"},{"issue":"1","key":"pntd.0010588.ref034","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1186\/s12916-018-1067-x","article-title":"Zika vaccines and therapeutics: landscape analysis and challenges ahead","volume":"16","author":"A Wilder-Smith","year":"2018","journal-title":"BMC medicine"},{"issue":"6507","key":"pntd.0010588.ref035","doi-asserted-by":"crossref","first-page":"1123","DOI":"10.1126\/science.abb6143","article-title":"Zika virus infection enhances future risk of severe dengue disease","volume":"369","author":"LC Katzelnick","year":"2020","journal-title":"Science (New York, NY)"},{"issue":"3","key":"pntd.0010588.ref036","doi-asserted-by":"crossref","first-page":"e29957","DOI":"10.1371\/journal.pone.0029957","article-title":"Antibodies against the envelope glycoprotein promote infectivity of immature dengue virus serotype 2","volume":"7","author":"JM da Silva Voorham","year":"2012","journal-title":"PloS one"},{"issue":"5979","key":"pntd.0010588.ref037","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1126\/science.1185181","article-title":"Cross-reacting antibodies enhance dengue virus infection in humans","volume":"328","author":"W Dejnirattisai","year":"2010","journal-title":"Science (New York, NY)"},{"issue":"62","key":"pntd.0010588.ref038","doi-asserted-by":"crossref","first-page":"106050","DOI":"10.18632\/oncotarget.22525","article-title":"TLR2\/MyD88 pathway-dependent regulation of dendritic cells by dengue virus promotes antibody-dependent enhancement via Th2-biased immunity","volume":"8","author":"JA George","year":"2017","journal-title":"Oncotarget"},{"key":"pntd.0010588.ref039","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1016\/S0065-3527(03)60011-4","article-title":"Neutralization and antibody-dependent enhancement of dengue viruses","volume":"60","author":"SB Halstead","year":"2003","journal-title":"Advances in virus research"},{"issue":"5","key":"pntd.0010588.ref040","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1007\/BF02255946","article-title":"Immunopathogenesis of dengue virus infection","volume":"8","author":"HY Lei","year":"2001","journal-title":"Journal of biomedical science"},{"issue":"1","key":"pntd.0010588.ref041","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1038\/nri2206","article-title":"Fcgamma receptors as regulators of immune responses","volume":"8","author":"F Nimmerjahn","year":"2008","journal-title":"Nature reviews Immunology"},{"issue":"4","key":"pntd.0010588.ref042","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1038\/s41577-019-0123-x","article-title":"Adaptive immune responses to primary and secondary dengue virus infections","volume":"19","author":"AL St John","year":"2019","journal-title":"Nature reviews Immunology"},{"key":"pntd.0010588.ref043","doi-asserted-by":"crossref","first-page":"102991","DOI":"10.1016\/j.ebiom.2020.102991","article-title":"Dengue and Zika virus infections are enhanced by live attenuated dengue vaccine but not by recombinant DSV4 vaccine candidate in mouse models","volume":"60","author":"R Shukla","year":"2020","journal-title":"EBioMedicine"},{"issue":"5","key":"pntd.0010588.ref044","doi-asserted-by":"crossref","first-page":"696","DOI":"10.1016\/j.chom.2016.04.013","article-title":"Structures of the Zika Virus Envelope Protein and Its Complex with a Flavivirus Broadly Protective Antibody","volume":"19","author":"L Dai","year":"2016","journal-title":"Cell Host Microbe"},{"issue":"5","key":"pntd.0010588.ref045","first-page":"311","article-title":"Observations related to pathogenesis of dengue hemorrhagic fever. IV. Relation of disease severity to antibody response and virus recovered","volume":"42","author":"SB Halstead","year":"1970","journal-title":"The Yale journal of biology and medicine"},{"issue":"7","key":"pntd.0010588.ref046","doi-asserted-by":"crossref","first-page":"1445","DOI":"10.1007\/s00705-013-1645-3","article-title":"Secondary infection as a risk factor for dengue hemorrhagic fever\/dengue shock syndrome: an historical perspective and role of antibody-dependent enhancement of infection","volume":"158","author":"MG Guzman","year":"2013","journal-title":"Archives of virology"},{"issue":"6","key":"pntd.0010588.ref047","doi-asserted-by":"crossref","first-page":"1342","DOI":"10.4269\/ajtmh.15-0337","article-title":"Forty Years of Dengue Surveillance at a Tertiary Pediatric Hospital in Bangkok, Thailand, 1973\u20132012","volume":"94","author":"A Nisalak","year":"2016","journal-title":"The American journal of tropical medicine and hygiene"},{"key":"pntd.0010588.ref048","unstructured":"DENGVAXIA. https:\/\/www.fda.gov\/vaccines-blood-biologics\/dengvaxia. Accessed on 26 July 2021. Updated on 01 January 2020."},{"key":"pntd.0010588.ref049","unstructured":"DENGVAXIA [updated 2020 Jan 01; accessed 2021 Jul 26]. https:\/\/www.fda.gov\/vaccines-blood-biologics\/dengvaxia."},{"issue":"93","key":"pntd.0010588.ref050","first-page":"457","volume":"36","year":"2018","journal-title":"Weekly epidemiological record"},{"issue":"35","key":"pntd.0010588.ref051","doi-asserted-by":"crossref","first-page":"4848","DOI":"10.1016\/j.vaccine.2018.09.063","article-title":"Dengue vaccine: WHO position paper, September 2018\u2014Recommendations","volume":"37","year":"2019","journal-title":"Vaccine"},{"issue":"9951","key":"pntd.0010588.ref052","doi-asserted-by":"crossref","first-page":"1358","DOI":"10.1016\/S0140-6736(14)61060-6","article-title":"Clinical efficacy and safety of a novel tetravalent dengue vaccine in healthy children in Asia: a phase 3, randomised, observer-masked, placebo-controlled trial","volume":"384","author":"MR Capeding","year":"2014","journal-title":"Lancet"},{"issue":"6","key":"pntd.0010588.ref053","doi-asserted-by":"crossref","first-page":"e0003749","DOI":"10.1371\/journal.pntd.0003749","article-title":"The Complexity of a Dengue Vaccine: A Review of the Human Antibody Response","volume":"9","author":"J Flipse","year":"2015","journal-title":"PLoS neglected tropical diseases"},{"issue":"13","key":"pntd.0010588.ref054","doi-asserted-by":"crossref","first-page":"1195","DOI":"10.1056\/NEJMoa1506223","article-title":"Efficacy and Long-Term Safety of a Dengue Vaccine in Regions of Endemic Disease","volume":"373","author":"SR Hadinegoro","year":"2015","journal-title":"The New England journal of medicine"},{"issue":"9853","key":"pntd.0010588.ref055","doi-asserted-by":"crossref","first-page":"1559","DOI":"10.1016\/S0140-6736(12)61428-7","article-title":"Protective efficacy of the recombinant, live-attenuated, CYD tetravalent dengue vaccine in Thai schoolchildren: a randomised, controlled phase 2b trial","volume":"380","author":"A Sabchareon","year":"2012","journal-title":"Lancet"},{"issue":"4","key":"pntd.0010588.ref056","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1056\/NEJMoa1800820","article-title":"Effect of Dengue Serostatus on Dengue Vaccine Safety and Efficacy","volume":"379","author":"S Sridhar","year":"2018","journal-title":"The New England journal of medicine"},{"key":"pntd.0010588.ref057","doi-asserted-by":"crossref","first-page":"1372","DOI":"10.3389\/fmicb.2017.01372","article-title":"Complexity of Human Antibody Response to Dengue Virus: Implication for Vaccine Development","volume":"8","author":"WY Tsai","year":"2017","journal-title":"Frontiers in microbiology"},{"issue":"2","key":"pntd.0010588.ref058","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1056\/NEJMoa1411037","article-title":"Efficacy of a tetravalent dengue vaccine in children in Latin America","volume":"372","author":"L Villar","year":"2015","journal-title":"The New England journal of medicine"},{"issue":"32, Part A","key":"pntd.0010588.ref059","doi-asserted-by":"crossref","first-page":"4768","DOI":"10.1016\/j.vaccine.2017.12.079","article-title":"Explanations for the high potency of HPV prophylactic vaccines","volume":"36","author":"J Schiller","year":"2018","journal-title":"Vaccine"},{"issue":"5138","key":"pntd.0010588.ref060","doi-asserted-by":"crossref","first-page":"1448","DOI":"10.1126\/science.8248784","article-title":"The influence of antigen organization on B cell responsiveness","volume":"262","author":"MF Bachmann","year":"1993","journal-title":"Science (New York, NY)"},{"key":"pntd.0010588.ref061","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.ebiom.2017.12.010","article-title":"Passive Transfer of Immune Sera Induced by a Zika Virus-Like Particle Vaccine Protects AG129 Mice Against Lethal Zika Virus Challenge","volume":"27","author":"D Espinosa","year":"2018","journal-title":"EBioMedicine"},{"issue":"3","key":"pntd.0010588.ref062","doi-asserted-by":"crossref","first-page":"e0009195","DOI":"10.1371\/journal.pntd.0009195","article-title":"Zika virus-like particle vaccine protects AG129 mice and rhesus macaques against Zika virus","volume":"15","author":"L Vang","year":"2021","journal-title":"PLoS neglected tropical diseases"},{"issue":"Suppl","key":"pntd.0010588.ref063","doi-asserted-by":"crossref","first-page":"S42","DOI":"10.1016\/j.jip.2011.05.004","article-title":"Large-scale production and purification of VLP-based vaccines","volume":"107","author":"T Vicente","year":"2011","journal-title":"J Invertebr Pathol"},{"issue":"23","key":"pntd.0010588.ref064","doi-asserted-by":"crossref","DOI":"10.1128\/JVI.01181-17","article-title":"An Envelope-Modified Tetravalent Dengue Virus-Like-Particle Vaccine Has Implications for Flavivirus Vaccine Design","volume":"91","author":"A Urakami","year":"2017","journal-title":"Journal of virology"},{"key":"pntd.0010588.ref065","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1186\/1471-2334-14-246","article-title":"Distinguishing West Nile virus infection using a recombinant envelope protein with mutations in the conserved fusion-loop","volume":"14","author":"S Chabierski","year":"2014","journal-title":"BMC infectious diseases"},{"key":"pntd.0010588.ref066","doi-asserted-by":"crossref","first-page":"334","DOI":"10.3389\/fimmu.2012.00334","article-title":"Sculpting humoral immunity through dengue vaccination to enhance protective immunity","volume":"3","author":"WD Crill","year":"2012","journal-title":"Frontiers in immunology"},{"issue":"13","key":"pntd.0010588.ref067","doi-asserted-by":"crossref","first-page":"6631","DOI":"10.1128\/JVI.00316-08","article-title":"Antibodies to envelope glycoprotein of dengue virus during the natural course of infection are predominantly cross-reactive and recognize epitopes containing highly conserved residues at the fusion loop of domain II","volume":"82","author":"CY Lai","year":"2008","journal-title":"Journal of virology"},{"issue":"14","key":"pntd.0010588.ref068","doi-asserted-by":"crossref","first-page":"8828","DOI":"10.1128\/JVI.79.14.8828-8834.2005","article-title":"A human T-cell leukemia virus type 1 regulatory element enhances the immunogenicity of human immunodeficiency virus type 1 DNA vaccines in mice and nonhuman primates","volume":"79","author":"DH Barouch","year":"2005","journal-title":"Journal of virology"},{"issue":"2","key":"pntd.0010588.ref069","doi-asserted-by":"crossref","DOI":"10.1084\/jem.20191792","article-title":"Mechanism of differential Zika and dengue virus neutralization by a public antibody lineage targeting the DIII lateral ridge","volume":"217","author":"H Zhao","year":"2020","journal-title":"The Journal of experimental medicine"},{"issue":"7633","key":"pntd.0010588.ref070","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1038\/nature20564","article-title":"Neutralizing human antibodies prevent Zika virus replication and fetal disease in mice","volume":"540","author":"G Sapparapu","year":"2016","journal-title":"Nature"},{"key":"pntd.0010588.ref071","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1016\/j.omtm.2020.06.011","article-title":"Intramuscular Delivery of Replicon RNA Encoding ZIKV-117 Human Monoclonal Antibody Protects against Zika Virus Infection","volume":"18","author":"JH Erasmus","year":"2020","journal-title":"Molecular therapy Methods & clinical development"},{"key":"pntd.0010588.ref072","doi-asserted-by":"crossref","first-page":"14722","DOI":"10.1038\/ncomms14722","article-title":"A human antibody against Zika virus crosslinks the E protein to prevent infection","volume":"8","author":"SS Hasan","year":"2017","journal-title":"Nat Commun"},{"issue":"4","key":"pntd.0010588.ref073","doi-asserted-by":"crossref","first-page":"1016","DOI":"10.1016\/j.cell.2016.07.020","article-title":"Structural Basis of Zika Virus-Specific Antibody Protection","volume":"166","author":"H Zhao","year":"2016","journal-title":"Cell"},{"issue":"11","key":"pntd.0010588.ref074","doi-asserted-by":"crossref","first-page":"e0008730","DOI":"10.1371\/journal.pntd.0008730","article-title":"Antigenicity, stability, and reproducibility of Zika reporter virus particles for long-term applications","volume":"14","author":"JC Whitbeck","year":"2020","journal-title":"PLoS neglected tropical diseases"},{"issue":"2","key":"pntd.0010588.ref075","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/j.chom.2016.07.002","article-title":"Zika Virus Targets Different Primary Human Placental Cells, Suggesting Two Routes for Vertical Transmission","volume":"20","author":"T Tabata","year":"2016","journal-title":"Cell Host Microbe"},{"issue":"6","key":"pntd.0010588.ref076","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1038\/s41577-021-00550-x","article-title":"Prospects for durable immune control of SARS-CoV-2 and prevention of reinfection","volume":"21","author":"D Cromer","year":"2021","journal-title":"Nature reviews Immunology"},{"key":"pntd.0010588.ref077","doi-asserted-by":"crossref","first-page":"571481","DOI":"10.3389\/fimmu.2020.571481","article-title":"Will SARS-CoV-2 Infection Elicit Long-Lasting Protective or Sterilising Immunity? Implications for Vaccine Strategies (2020)","volume":"11","author":"DS Kim","year":"2020","journal-title":"Frontiers in immunology"},{"key":"pntd.0010588.ref078","doi-asserted-by":"crossref","first-page":"112282","DOI":"10.1016\/j.biopha.2021.112282","article-title":"Sterilizing Immunity against COVID-19: Developing Helper T cells I and II activating vaccines is imperative","volume":"144","author":"I Kyei-Barffour","year":"2021","journal-title":"Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie"},{"issue":"12","key":"pntd.0010588.ref079","doi-asserted-by":"crossref","first-page":"6189","DOI":"10.4049\/jimmunol.168.12.6189","article-title":"A decaepitope polypeptide primes for multiple CD8+ IFN-gamma and Th lymphocyte responses: evaluation of multiepitope polypeptides as a mode for vaccine delivery","volume":"168","author":"J Alexander","year":"2002","journal-title":"Journal of immunology (Baltimore, Md: 1950)"},{"issue":"2","key":"pntd.0010588.ref080","doi-asserted-by":"crossref","DOI":"10.3390\/v14020242","article-title":"Current Understanding of the Role of T Cells in Chikungunya, Dengue and Zika Infections","volume":"14","author":"M Mapalagamage","year":"2022","journal-title":"Viruses"},{"issue":"12","key":"pntd.0010588.ref081","doi-asserted-by":"crossref","first-page":"3487","DOI":"10.4049\/jimmunol.1801090","article-title":"Cutting Edge: Transcriptional Profiling Reveals Multifunctional and Cytotoxic Antiviral Responses of Zika Virus-Specific CD8(+) T Cells","volume":"201","author":"A Grifoni","year":"2018","journal-title":"Journal of immunology (Baltimore, Md: 1950)"},{"issue":"6","key":"pntd.0010588.ref082","doi-asserted-by":"crossref","DOI":"10.3390\/vaccines9060671","article-title":"What Constitutes Protective Immunity Following Yellow Fever Vaccination?","volume":"9","author":"J Mokaya","year":"2021","journal-title":"Vaccines"},{"issue":"35","key":"pntd.0010588.ref083","doi-asserted-by":"crossref","first-page":"6008","DOI":"10.1016\/j.vaccine.2011.06.034","article-title":"Immune correlates of protection against yellow fever determined by passive immunization and challenge in the hamster model","volume":"29","author":"JG Julander","year":"2011","journal-title":"Vaccine"},{"issue":"9","key":"pntd.0010588.ref084","article-title":"The Present and Future of Yellow Fever Vaccines","volume":"14","author":"CA Hansen","year":"2021","journal-title":"Pharmaceuticals (Basel, Switzerland)"},{"issue":"3","key":"pntd.0010588.ref085","doi-asserted-by":"crossref","first-page":"e0149871","DOI":"10.1371\/journal.pone.0149871","article-title":"A Single 17D Yellow Fever Vaccination Provides Lifelong Immunity; Characterization of Yellow-Fever-Specific Neutralizing Antibody and T-Cell Responses after Vaccination","volume":"11","author":"RW Wieten","year":"2016","journal-title":"PloS one"},{"issue":"5","key":"pntd.0010588.ref086","doi-asserted-by":"crossref","DOI":"10.1128\/JVI.02147-16","article-title":"Human CD4(+) T Cell Responses to an Attenuated Tetravalent Dengue Vaccine Parallel Those Induced by Natural Infection in Magnitude, HLA Restriction, and Antigen Specificity","volume":"91","author":"MA Angelo","year":"2017","journal-title":"Journal of virology"},{"issue":"11","key":"pntd.0010588.ref087","doi-asserted-by":"crossref","first-page":"1479","DOI":"10.1586\/14760584.2015.1083430","article-title":"Current status and future prospects of yellow fever vaccines","volume":"14","author":"AS Beck","year":"2015","journal-title":"Expert review of vaccines"},{"issue":"4","key":"pntd.0010588.ref088","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1128\/am.25.4.539-544.1973","article-title":"Yellow fever vaccine: direct challenge of monkeys given graded doses of 17D vaccine","volume":"25","author":"RA Mason","year":"1973","journal-title":"Applied microbiology"},{"issue":"6","key":"pntd.0010588.ref089","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/21645515.2017.1285472","article-title":"Japanese encephalitis vaccines: Immunogenicity, protective efficacy, effectiveness, and impact on the burden of disease","volume":"13","author":"NR Hegde","year":"2017","journal-title":"Human vaccines & immunotherapeutics"},{"issue":"35","key":"pntd.0010588.ref090","doi-asserted-by":"crossref","first-page":"5925","DOI":"10.1016\/j.vaccine.2011.06.062","article-title":"Correlation of protection against Japanese encephalitis virus and JE vaccine (IXIARO) induced neutralizing antibody titers","volume":"29","author":"Y Van Gessel","year":"2011","journal-title":"Vaccine"},{"issue":"3","key":"pntd.0010588.ref091","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1046\/j.1365-2249.1997.4311446.x","article-title":"Antibodies protect mice against challenge with tick-borne encephalitis virus (TBEV)-infected macrophages","volume":"110","author":"TR Kreil","year":"1997","journal-title":"Clinical and experimental immunology"},{"key":"#cr-split#-pntd.0010588.ref092.1","unstructured":"Poehling and Hills TBE vaccine presentation 2021 [updated 2021 Sep 29"},{"key":"#cr-split#-pntd.0010588.ref092.2","unstructured":"accessed 2022 Apr 27]. https:\/\/www.cdc.gov\/vaccines\/acip\/meetings\/downloads\/slides-2021-09-29\/01-TBE-Poehling-and-Hills-508.pdf."},{"key":"pntd.0010588.ref093","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/S0065-3527(03)59005-4","article-title":"Antigenic structure of flavivirus proteins","volume":"59","author":"JT Roehrig","year":"2003","journal-title":"Advances in virus research"},{"issue":"6301","key":"pntd.0010588.ref094","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1126\/science.aaf8505","article-title":"Specificity, cross-reactivity, and function of antibodies elicited by Zika virus infection","volume":"353","author":"K Stettler","year":"2016","journal-title":"Science (New York, NY)"},{"issue":"15","key":"pntd.0010588.ref095","doi-asserted-by":"crossref","first-page":"6779","DOI":"10.1007\/s00253-020-10710-z","article-title":"T cell immunity rather than antibody mediates cross-protection against Zika virus infection conferred by a live attenuated Japanese encephalitis SA14-14-2 vaccine","volume":"104","author":"R Wang","year":"2020","journal-title":"Appl Microbiol Biotechnol"},{"issue":"12","key":"pntd.0010588.ref096","article-title":"Delineating antibody recognition against Zika virus during natural infection","volume":"2","author":"L Yu","year":"2017","journal-title":"JCI Insight"},{"issue":"9","key":"pntd.0010588.ref097","doi-asserted-by":"crossref","first-page":"5816","DOI":"10.1128\/jvi.69.9.5816-5820.1995","article-title":"Synthesis and secretion of recombinant tick-borne encephalitis virus protein E in soluble and particulate form","volume":"69","author":"SL Allison","year":"1995","journal-title":"Journal of virology"},{"key":"pntd.0010588.ref098","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1146\/annurev-med-121217-094234","article-title":"Structure-Based Vaccine Antigen Design","volume":"70","author":"BS Graham","year":"2019","journal-title":"Annual review of medicine"},{"key":"pntd.0010588.ref099","article-title":"Epitope resurfacing on dengue virus-like particle vaccine preparation to induce broad neutralizing antibody","volume":"7","author":"WF Shen","year":"2018","journal-title":"eLife"},{"issue":"1","key":"pntd.0010588.ref100","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1073\/pnas.1819607116","article-title":"Insights from direct studies on human dengue infections","volume":"116","author":"SB Halstead","year":"2019","journal-title":"Proceedings of the National Academy of Sciences"},{"issue":"1","key":"pntd.0010588.ref101","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1146\/annurev-virology-092917-043300","article-title":"The Many Faces of a Dynamic Virion: Implications of Viral Breathing on Flavivirus Biology and Immunogenicity","volume":"5","author":"KA Dowd","year":"2018","journal-title":"Annu Rev Virol"},{"issue":"3","key":"pntd.0010588.ref102","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1016\/S1097-2765(01)00206-4","article-title":"Molecular organization of a recombinant subviral particle from tick-borne encephalitis virus","volume":"7","author":"I Ferlenghi","year":"2001","journal-title":"Molecular cell"},{"issue":"40","key":"pntd.0010588.ref103","doi-asserted-by":"crossref","first-page":"6588","DOI":"10.1016\/j.vaccine.2010.07.055","article-title":"Immunogenicity and efficacy of two types of West Nile virus-like particles different in size and maturation as a second-generation vaccine candidate","volume":"28","author":"N Ohtaki","year":"2010","journal-title":"Vaccine"},{"issue":"1","key":"pntd.0010588.ref104","doi-asserted-by":"crossref","first-page":"895","DOI":"10.1038\/s41467-020-14647-9","article-title":"Capsid protein structure in Zika virus reveals the flavivirus assembly process","volume":"11","author":"TY Tan","year":"2020","journal-title":"Nat Commun"},{"issue":"1","key":"pntd.0010588.ref105","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1186\/s12879-018-3572-0","article-title":"Cross-reactive dengue virus-derived monoclonal antibodies to Zika virus envelope protein: Panacea or Pandora\u2019s box?","volume":"18","author":"SA Gunawardana","year":"2018","journal-title":"BMC infectious diseases"},{"issue":"5","key":"pntd.0010588.ref106","first-page":"781","article-title":"Dengue Virus-Specific Antibodies Enhance Brazilian Zika Virus Infection","volume":"215","author":"PMS Castanha","year":"2017","journal-title":"The Journal of infectious diseases"},{"issue":"2","key":"pntd.0010588.ref107","doi-asserted-by":"crossref","first-page":"266","DOI":"10.3390\/vaccines8020266","article-title":"Current Status of Zika Virus Vaccines: Successes and Challenges","volume":"8","author":"A Pattnaik","year":"2020","journal-title":"Vaccines (Basel)"},{"issue":"9","key":"pntd.0010588.ref108","doi-asserted-by":"crossref","first-page":"1102","DOI":"10.1038\/ni.3515","article-title":"Dengue virus sero-cross-reactivity drives antibody-dependent enhancement of infection with zika virus","volume":"17","author":"W Dejnirattisai","year":"2016","journal-title":"Nature immunology"},{"key":"pntd.0010588.ref109","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2021.717425","article-title":"The Ability of Zika virus Intravenous Immunoglobulin to Protect From or Enhance Zika Virus Disease","volume":"12","author":"AK Pinto","year":"2021","journal-title":"Frontiers in immunology"},{"issue":"1","key":"pntd.0010588.ref110","doi-asserted-by":"crossref","first-page":"15674","DOI":"10.1038\/ncomms15674","article-title":"Zika virus pathogenesis in rhesus macaques is unaffected by pre-existing immunity to dengue virus","volume":"8","author":"P Pantoja","year":"2017","journal-title":"Nat Commun"},{"issue":"44","key":"pntd.0010588.ref111","doi-asserted-by":"crossref","first-page":"5134","DOI":"10.1016\/j.vaccine.2013.08.027","article-title":"Generation and preclinical evaluation of a DENV-1\/2 prM+E chimeric live attenuated vaccine candidate with enhanced prM cleavage","volume":"31","author":"P Keelapang","year":"2013","journal-title":"Vaccine"},{"issue":"42","key":"pntd.0010588.ref112","doi-asserted-by":"crossref","first-page":"5613","DOI":"10.1016\/j.vaccine.2015.08.090","article-title":"Generation and preclinical immunogenicity study of dengue type 2 virus-like particles derived from stably transfected mosquito cells","volume":"33","author":"A Suphatrakul","year":"2015","journal-title":"Vaccine"},{"issue":"1","key":"pntd.0010588.ref113","doi-asserted-by":"crossref","first-page":"4524","DOI":"10.1038\/s41598-017-04767-6","article-title":"In Vitro Assembly and Stabilization of Dengue and Zika Virus Envelope Protein Homo-Dimers","volume":"7","author":"SW Metz","year":"2017","journal-title":"Sci Rep"},{"issue":"8","key":"pntd.0010588.ref114","doi-asserted-by":"crossref","first-page":"958","DOI":"10.1038\/s41590-021-00966-6","article-title":"Protective Zika vaccines engineered to eliminate enhancement of dengue infection via immunodominance switch","volume":"22","author":"L Dai","year":"2021","journal-title":"Nature Immunology"},{"key":"pntd.0010588.ref115","doi-asserted-by":"crossref","first-page":"15411","DOI":"10.1038\/ncomms15411","article-title":"Covalently linked dengue virus envelope glycoprotein dimers reduce exposure of the immunodominant fusion loop epitope","volume":"8","author":"A Rouvinski","year":"2017","journal-title":"Nat Commun"},{"issue":"3","key":"pntd.0010588.ref116","doi-asserted-by":"crossref","first-page":"e0003564","DOI":"10.1371\/journal.pntd.0003564","article-title":"Antibodies against immature virions are not a discriminating factor for dengue disease severity","volume":"9","author":"IA Rodenhuis-Zybert","year":"2015","journal-title":"PLoS neglected tropical diseases"}],"updated-by":[{"DOI":"10.1371\/journal.pntd.0010588","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2022,7,18]],"date-time":"2022-07-18T00:00:00Z","timestamp":1658102400000}}],"container-title":["PLOS Neglected Tropical Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pntd.0010588","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,7,18]],"date-time":"2022-07-18T17:39:19Z","timestamp":1658165959000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pntd.0010588"}},"subtitle":[],"editor":[{"given":"Helene","family":"Dutartre","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2022,7,6]]},"references-count":117,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2022,7,6]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pntd.0010588","relation":{"new_version":[{"id-type":"doi","id":"10.1371\/journal.pntd.0010588","asserted-by":"object"}]},"ISSN":["1935-2735"],"issn-type":[{"value":"1935-2735","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,7,6]]}}}