{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T10:01:51Z","timestamp":1773741711163,"version":"3.50.1"},"reference-count":43,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,2,28]],"date-time":"2023-02-28T00:00:00Z","timestamp":1677542400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Virol."],"abstract":"<jats:p>Zika virus (ZIKV) is a mosquito-borne flavivirus that causes an acute febrile illness. ZIKV can be transmitted between sexual partners and from mother to fetus. Infection is strongly associated with neurologic complications in adults, including Guillain-Barr\u00e9 syndrome and myelitis, and congenital ZIKV infection can result in fetal injury and congenital Zika syndrome (CZS). Development of an effective vaccine is imperative to protect against ZIKV vertical transmission and CZS. Recombinant Vesicular Stomatitis virus (rVSV) is a highly effective and safe vector for the delivery of foreign immunogens for vaccine purposes. Here, we evaluate an rVSV vaccine expressing the full length pre-membrane (prM) and ZIKV envelope (E) proteins (rVSV\u0394M-ZprME), shown to be immunogenic in murine models of ZIKV infection, for its capacity to induce immune responses in nonhuman primates. Moreover, we assess the efficacy of the rVSV\u0394M-ZprME vaccine in the protection of pigtail macaques against ZIKV infection. Administration of the rVSV\u0394M-ZprME vaccine was safe, but it did not induce robust anti-ZIKV T-cell responses, IgM or IgG antibodies, or neutralizing antibodies in most animals. Post ZIKV challenge, animals that received the rVSV\u0394M control vaccine lacking ZIKV antigen had higher levels of plasma viremia compared to animals that received the rVSV\u0394M-ZprME vaccine. Anti-ZIKV neutralizing Ab titers were detected in a single animal that received the rVSV\u0394M-ZprME vaccine that was associated with reduced plasma viremia. The overall suboptimal ZIKV-specific cellular and humoral responses post-immunization indicates the rVSV\u0394M-ZprME vaccine did not elicit an immune response in this pilot study. However, recall antibody response to the rVSV\u0394M-ZprME vaccine indicates it may be immunogenic and further developments to the vaccine construct could enhance its potential as a vaccine candidate in a nonhuman primate pre-clinical model.<\/jats:p>","DOI":"10.3389\/fviro.2023.1108420","type":"journal-article","created":{"date-parts":[[2023,3,6]],"date-time":"2023-03-06T16:59:56Z","timestamp":1678121996000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["Evaluation of the immunogenicity and efficacy of an rVSV vaccine against Zika virus infection in macaca nemestrina"],"prefix":"10.3389","volume":"3","author":[{"given":"Jennifer","family":"Tisoncik-Go","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kathleen M.","family":"Voss","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas B.","family":"Lewis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonio E.","family":"Muruato","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"LaRene","family":"Kuller","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eric E.","family":"Finn","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dillon","family":"Betancourt","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Solomon","family":"Wangari","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joel","family":"Ahrens","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naoto","family":"Iwayama","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard F.","family":"Grant","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert D.","family":"Murnane","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul T.","family":"Edlefsen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Deborah H.","family":"Fuller","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Glen N.","family":"Barber","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"suffix":"Jr","given":"Michael","family":"Gale","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Megan A.","family":"O\u2019Connor","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2023,2,28]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1007\/s00705-006-0903-z","article-title":"Full-length sequencing and genomic characterization of bagaza, kedougou, and zika viruses","volume":"152","author":"Kuno","year":"2007","journal-title":"Arch Virol"},{"key":"B2","doi-asserted-by":"publisher","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":"Dai","year":"2016","journal-title":"Cell Host Microbe"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01469-17","article-title":"Prior dengue virus exposure shapes T cell immunity to zika virus in humans","volume":"91","author":"Grifoni","year":"2017","journal-title":"J Virol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaf8505","article-title":"Specificity, cross-reactivity, and function of antibodies elicited by zika virus infection","volume":"353","author":"Stettler","year":"2016","journal-title":"Science"},{"key":"B5","doi-asserted-by":"publisher","first-page":"3360","DOI":"10.1016\/j.celrep.2019.02.062","article-title":"Structural basis for neutralization and protection by a zika virus-specific human antibody","volume":"26","author":"Wang","year":"2019","journal-title":"Cell Rep"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.774026","article-title":"Single dose of a VSV-based vaccine rapidly protects macaques from marburg virus disease","volume":"12","author":"Marzi","year":"2021","journal-title":"Front Immunol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaut.2016.12.007","article-title":"A comprehensive analysis and immunobiology of autoimmune neurological syndromes during the zika virus outbreak in cucuta, Colombia","volume":"77","author":"Anaya","year":"2017","journal-title":"J Autoimmun"},{"key":"B8","doi-asserted-by":"publisher","first-page":"1482","DOI":"10.1016\/S0140-6736(16)30058-7","article-title":"Guillain-Barre syndrome associated with zika virus infection","volume":"387","author":"Brasil","year":"2016","journal-title":"Lancet"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1001\/jamapediatrics.2016.3982","article-title":"Characterizing the pattern of anomalies in congenital zika syndrome for pediatric clinicians","volume":"171","author":"Moore","year":"2017","journal-title":"JAMA pediatrics."},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0005869","article-title":"Increased rates of Guillain-barre syndrome associated with zika virus outbreak in the Salvador metropolitan area, Brazil","volume":"11","author":"Styczynski","year":"2017","journal-title":"PloS Negl Trop Dis"},{"key":"B11","doi-asserted-by":"publisher","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":"Gaudinski","year":"2018","journal-title":"Lancet"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1126\/science.aai9137","article-title":"Rapid development of a DNA vaccine for zika virus","volume":"354","author":"Dowd","year":"2016","journal-title":"Science"},{"key":"B13","doi-asserted-by":"publisher","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":"Modjarrad","year":"2018","journal-title":"Lancet"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.4269\/ajtmh.2001.65.405","article-title":"Attenuation and immunogenicity in humans of a live dengue virus type-4 vaccine candidate with a 30 nucleotide deletion in its 3'-untranslated region","volume":"65","author":"Durbin","year":"2001","journal-title":"Am J Trop Med Hyg"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1038\/nature21428","article-title":"Zika virus protection by a single low-dose nucleoside-modified mRNA vaccination","volume":"543","author":"Pardi","year":"2017","journal-title":"Nature"},{"key":"B16","doi-asserted-by":"publisher","first-page":"895","DOI":"10.1128\/JVI.76.2.895-904.2002","article-title":"Genetically engineered vesicular stomatitis virus in gene therapy: Application for treatment of malignant disease","volume":"76","author":"Fernandez","year":"2002","journal-title":"J Virol"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1080\/713803696","article-title":"Vesicular stomatitis virus (VSV) therapy of tumors","volume":"50","author":"Balachandran","year":"2000","journal-title":"IUBMB Life"},{"key":"B18","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1016\/j.omto.2018.12.001","article-title":"Enhanced safety and efficacy of oncolytic VSV therapy by combination with T cell receptor transgenic T cells as carriers","volume":"12","author":"Melzer","year":"2019","journal-title":"Mol Ther Oncolytics."},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1502924","article-title":"Phase 1 trials of rVSV Ebola vaccine in Africa and Europe","volume":"374","author":"Agnandji","year":"2016","journal-title":"N Engl J Med"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(16)32621-6","article-title":"Efficacy and effectiveness of an rVSV-vectored vaccine in preventing Ebola virus disease: Final results from the Guinea ring vaccination, open-label, cluster-randomised trial (Ebola Ca suffit!)","volume":"389","author":"Henao-Restrepo","year":"2017","journal-title":"Lancet"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.15585\/mmwr.mm7108a2","article-title":"Use of Ebola vaccine: Expansion of recommendations of the advisory committee on immunization practices to include two additional populations - united states, 2021","volume":"71","author":"Malenfant","year":"2022","journal-title":"MMWR Morb Mortal Wkly Rep"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1414216","article-title":"A recombinant vesicular stomatitis virus Ebola vaccine","volume":"376","author":"Regules","year":"2017","journal-title":"N Engl J Med"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.01337-22","article-title":"A recombinant VSV-based bivalent vaccine effectively protects against both SARS-CoV-2 and influenza a virus infection","volume":"96","author":"Ao","year":"2022","journal-title":"J Virol"},{"key":"B24","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1038\/s41541-019-0155-z","article-title":"A single dose of a vesicular stomatitis virus-based influenza vaccine confers rapid protection against H5 viruses from different clades","volume":"5","author":"Furuyama","year":"2020","journal-title":"NPJ Vaccines"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1101\/2021.01.19.426885","article-title":"Rapid protection from COVID-19 in nonhuman primates vaccinated intramuscularly but not intranasally with a single dose of a vesicular stomatitis virus-based vaccine","volume":"2022","author":"Furuyama","year":"2022","journal-title":"mBio"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.3390\/vaccines10030435","article-title":"VSV-based vaccines reduce virus shedding and viral load in hamsters infected with SARS-CoV-2 variants of concern","volume":"10","author":"O'Donnell","year":"2022","journal-title":"Vaccines (Basel)."},{"key":"B27","doi-asserted-by":"publisher","first-page":"893","DOI":"10.1016\/j.vaccine.2008.11.087","article-title":"Recombinant vesicular stomatitis virus-based west Nile vaccine elicits strong humoral and cellular immune responses and protects mice against lethal challenge with the virulent west Nile virus strain LSU-AR01","volume":"27","author":"Iyer","year":"2009","journal-title":"Vaccine"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.20.22.8590-8601.2000","article-title":"The matrix protein of vesicular stomatitis virus inhibits nucleocytoplasmic transport when it is in the nucleus and associated with nuclear pore complexes","volume":"20","author":"Petersen","year":"2000","journal-title":"Mol Cell Biol"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1602180","article-title":"Cutting edge: Innate immune augmenting vesicular stomatitis virus expressing zika virus proteins confers protective immunity","volume":"198","author":"Betancourt","year":"2017","journal-title":"J Immunol"},{"key":"B30","doi-asserted-by":"publisher","first-page":"3371","DOI":"10.1038\/s41467-018-05826-w","article-title":"Early cellular innate immune responses drive zika viral persistence and tissue tropism in pigtail macaques","volume":"9","author":"O'Connor","year":"2018","journal-title":"Nat Commun"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1038\/nm.4485","article-title":"Congenital zika virus infection as a silent pathology with loss of neurogenic output in the fetal brain","volume":"24","author":"Adams Waldorf","year":"2018","journal-title":"Nat Med"},{"key":"B32","doi-asserted-by":"publisher","first-page":"113671","DOI":"10.1016\/j.jviromet.2019.05.011","article-title":"Performance of InBios ZIKV detect 2.0 IgM capture ELISA in two reference laboratories compared to the original ZIKV detect IgM capture ELISA","volume":"271","author":"Basile","year":"2019","journal-title":"J Virol Methods"},{"key":"B33","doi-asserted-by":"publisher","first-page":"597","DOI":"10.1016\/j.cell.2017.04.024","article-title":"Recurrent potent human neutralizing antibodies to zika virus in Brazil and Mexico","volume":"169","author":"Robbiani","year":"2017","journal-title":"Cell"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00640-19","article-title":"Comparative analysis of African and Asian lineage-derived zika virus strains reveals differences in activation of and sensitivity to antiviral innate immunity","volume":"93","author":"Esser-Nobis","year":"2019","journal-title":"J Virol"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2016.06.071","article-title":"Live virus vaccines based on a vesicular stomatitis virus (VSV) backbone: Standardized template with key considerations for a risk\/benefit assessment","volume":"34","author":"Clarke","year":"2016","journal-title":"Vaccine"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1503\/cmaj.170074","article-title":"Assessing the safety and immunogenicity of recombinant vesicular stomatitis virus Ebola vaccine in healthy adults: a randomized clinical trial","volume":"189","author":"ElSherif","year":"2017","journal-title":"CMAJ"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jix336","article-title":"Rapid establishment of a cold chain capacity of -60 degrees c or colder for the STRIVE Ebola vaccine trial during the Ebola outbreak in Sierra Leone","volume":"217","author":"Jusu","year":"2018","journal-title":"J Infect Dis"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.3201\/eid2508.190281","article-title":"Evaluating temperature sensitivity of vesicular stomatitis virus-based vaccines","volume":"25","author":"Stein","year":"2019","journal-title":"Emerg Infect Dis"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1209591110","article-title":"Antibodies are necessary for rVSV\/ZEBOV-GP-mediated protection against lethal Ebola virus challenge in nonhuman primates","volume":"110","author":"Marzi","year":"2013","journal-title":"Proc Natl Acad Sci U S A."},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.00597-19","article-title":"Antiviral innate responses induced by VSV-EBOV vaccination contribute to rapid protection","volume":"10","author":"Menicucci","year":"2019","journal-title":"mBio"},{"key":"B41","doi-asserted-by":"publisher","first-page":"11043","DOI":"10.1038\/s41598-018-29401-x","article-title":"A VSV-based zika virus vaccine protects mice from lethal challenge","volume":"8","author":"Emanuel","year":"2018","journal-title":"Sci Rep"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2019.09.055","article-title":"Single low-dose VSV-EBOV vaccination protects cynomolgus macaques from lethal Ebola challenge","volume":"49","author":"Marzi","year":"2019","journal-title":"EBioMedicine"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1038\/nm.4193","article-title":"Fetal brain lesions after subcutaneous inoculation of zika virus in a pregnant nonhuman primate","volume":"22","author":"Adams Waldorf","year":"2016","journal-title":"Nat Med"}],"container-title":["Frontiers in Virology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fviro.2023.1108420\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,3,6]],"date-time":"2023-03-06T16:59:59Z","timestamp":1678121999000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fviro.2023.1108420\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,2,28]]},"references-count":43,"alternative-id":["10.3389\/fviro.2023.1108420"],"URL":"https:\/\/doi.org\/10.3389\/fviro.2023.1108420","relation":{},"ISSN":["2673-818X"],"issn-type":[{"value":"2673-818X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,2,28]]},"article-number":"1108420"}}