{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T14:57:36Z","timestamp":1787497056315,"version":"build-2736575974"},"reference-count":49,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2022,6,1]],"date-time":"2022-06-01T00:00:00Z","timestamp":1654041600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Medical Virology"],"published-print":{"date-parts":[[2022,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    The constantly emerging severe acute respiratory syndrome\u2010coronavirus 2 (SARS\u2010CoV\u20102) variants of concerns (VOCs) with mutations in the receptor\u2010binding domain (RBD) spread rapidly and has become a severe public health problem worldwide. Effective vaccines and optimized booster vaccination strategies are thus highly required. Here, the gene encoding six different RBD (Alpha, Beta, Gamma, Kappa, Delta, and Epsilon variants) along with the Fc fragment of human IgG1 (RBD\u2010Fc) was cloned into plant expression vector and produced in\n                    <jats:italic>Nicotiana benthamiana<\/jats:italic>\n                    by transient expression. Further, the immunogenicity of plant\u2010produced variant RBD\u2010Fc fusion proteins were tested in cynomolgus monkeys. Each group of cynomolgus monkeys was immunized three times intramuscularly with variant RBD\u2010Fc vaccines at Day 0, 21, 42, and neutralizing antibody responses were evaluated against ancestral (Wuhan), Alpha, Beta, Gamma, and Delta variants. The results showed that three doses of the RBD\u2010Fc vaccine significantly enhanced the immune response against all tested SARS\u2010CoV\u20102 variants. In particular, the vaccines based on Delta and Epsilon mutant RBD elicit broadly neutralizing antibodies against ancestral (Wuhan), Alpha, and Delta SARS\u2010CoV\u20102 variants whereas Beta and Gamma RBD\u2010Fc vaccines elicit neutralizing antibodies against their respective SARS\u2010CoV\u20102 strains. The Delta and Epsilon RBD\u2010Fc based vaccines displayed cross\u2010reactive immunogenicity and might be applied as a booster vaccine to induce broadly neutralizing antibodies. These proof\u2010of\u2010concept results will be helpful for the development of plant\u2010derived RBD\u2010Fc\u2010based vaccines against SARS\u2010CoV\u20102 and its variants.\n                  <\/jats:p>","DOI":"10.1002\/jmv.27881","type":"journal-article","created":{"date-parts":[[2022,5,26]],"date-time":"2022-05-26T03:40:49Z","timestamp":1653536449000},"page":"4265-4276","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Receptor binding domain proteins of SARS\u2010CoV\u20102 variants produced in\n                    <i>Nicotiana benthamiana<\/i>\n                    elicit neutralizing antibodies against variants of concern"],"prefix":"10.1002","volume":"94","author":[{"given":"Narach","family":"Khorattanakulchai","sequence":"first","affiliation":[{"name":"Center of Excellence in Plant\u2010produced Pharmaceuticals Chulalongkorn University Bangkok Thailand"},{"name":"Department of Pharmacognosy and Pharmaceutical Botany, Faculty of Pharmaceutical Sciences Chulalongkorn University Bangkok Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suwimon","family":"Manopwisedjaroen","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Faculty of Science Mahidol University Bangkok Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaewta","family":"Rattanapisit","sequence":"additional","affiliation":[{"name":"Baiya Phytopharm Co., Ltd Bangkok Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chalisa","family":"Panapitakkul","sequence":"additional","affiliation":[{"name":"Center of Excellence in Plant\u2010produced Pharmaceuticals Chulalongkorn University Bangkok Thailand"},{"name":"Department of Pharmacognosy and Pharmaceutical Botany, Faculty of Pharmaceutical Sciences Chulalongkorn University Bangkok Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taratorn","family":"Kemthong","sequence":"additional","affiliation":[{"name":"National Primate Research Center of Thailand Chulalongkorn University Saraburi Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nutchanat","family":"Suttisan","sequence":"additional","affiliation":[{"name":"National Primate Research Center of Thailand Chulalongkorn University Saraburi Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kanjana","family":"Srisutthisamphan","sequence":"additional","affiliation":[{"name":"Virology and Cell Technology Laboratory, National Center for Genetic Engineering and Biotechnology (BIOTEC) National Science and Technology Development Agency Pathumthani Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suchinda","family":"Malaivijitnond","sequence":"additional","affiliation":[{"name":"National Primate Research Center of Thailand Chulalongkorn University Saraburi Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arunee","family":"Thitithanyanont","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Faculty of Science Mahidol University Bangkok Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anan","family":"Jongkaewwattana","sequence":"additional","affiliation":[{"name":"Virology and Cell Technology Laboratory, National Center for Genetic Engineering and Biotechnology (BIOTEC) National Science and Technology Development Agency Pathumthani Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3861-4385","authenticated-orcid":false,"given":"Balamurugan","family":"Shanmugaraj","sequence":"additional","affiliation":[{"name":"Baiya Phytopharm Co., Ltd Bangkok Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5958-7406","authenticated-orcid":false,"given":"Waranyoo","family":"Phoolcharoen","sequence":"additional","affiliation":[{"name":"Center of Excellence in Plant\u2010produced Pharmaceuticals Chulalongkorn University Bangkok Thailand"},{"name":"Department of Pharmacognosy and Pharmaceutical Botany, Faculty of Pharmaceutical Sciences Chulalongkorn University Bangkok Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,6]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(20)30183-5"},{"key":"e_1_2_11_3_1","unstructured":"World Health Organization. WHO Director\u2010General's opening remarks at the media briefing on COVID\u201019 \u2010 11 March 2020. Accessed May 23 2022.https:\/\/www.who.int\/director-general\/speeches\/detail\/who-director-general-s-opening-remarks-at-the-media-briefing-on-covid-19---11-march-2020"},{"key":"e_1_2_11_4_1","unstructured":"World Health Organization. WHO coronavirus (COVID\u201019) dashboard.2020. Accessed May 23 2022.https:\/\/covid19.who.int\/"},{"key":"e_1_2_11_5_1","unstructured":"World Health Organization. DRAFT landscape of COVID\u201019 candidate vaccines.2021. Accessed May 23 2022.https:\/\/www.who.int\/publications\/m\/item\/draft-landscape-of-covid-19-candidate-vaccines"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2020.00298"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41423-020-0400-4"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.addr.2021.01.001"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2026920"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(21)00127-4"},{"key":"e_1_2_11_11_1","unstructured":"World Health Organization. Status of COVID\u201019 vaccines within WHO EUL\/PQ evaluation process. Accessed May 23 2022.https:\/\/extranet.who.int\/pqweb\/sites\/default\/files\/documents\/Status_COVID_VAX_02April2022.pdf"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMc2100362"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-021-01397-4"},{"key":"e_1_2_11_14_1","unstructured":"World Health Organization. Tracking SARS\u2010CoV\u20102 variants.2021. Accessed May 23 2022.https:\/\/www.who.int\/en\/activities\/tracking-SARS-CoV-2-variants\/"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmi.2021.10.005"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/jmv.27532"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-25479-6"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-03777-9"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciab1041"},{"issue":"2","key":"e_1_2_11_20_1","doi-asserted-by":"crossref","first-page":"49\u201051","DOI":"10.4103\/1995-7645.306736","article-title":"Addressing demand for recombinant biopharmaceuticals in the COVID\u201019 era","volume":"14","author":"Shanmugaraj B","year":"2021","journal-title":"Asian Pac J Trop Med"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tplants.2020.04.009"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.3390\/plants10061213"},{"key":"e_1_2_11_23_1","doi-asserted-by":"crossref","unstructured":"Lobato GomezM HuangX AlvarezD et al.Contributions of the international plant science community to the fight against human infectious diseases \u2010 part 1: epidemic and pandemic diseases.Plant Biotechnol J.2021.","DOI":"10.1111\/pbi.13657"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.3390\/pathogens10081051"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2005.01.006"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.3390\/v13010005"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.2174\/1389200218666170711121810"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.3390\/plants9070842"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-323-90248-9.00017-6"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.3389\/fpls.2020.589995"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-74904-1"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.3389\/fpls.2021.682953"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.3390\/vaccines9070744"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2006.10.031"},{"issue":"3","key":"e_1_2_11_35_1","first-page":"129","article-title":"A recombinant protein containing highly conserved hemagglutinin residues 81\u2010122 of influenza H5N1 induces strong humoral and mucosal immune responses","volume":"7","author":"Li Y","year":"2013","journal-title":"Biosci Trends"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0253574"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.4161\/hv.7.3.14262"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-1759(98)00170-7"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(21)00568-5"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.3390\/v12091011"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.3390\/mps1010008"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.70658"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2020.10.109"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-04245-0"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciab762"},{"key":"e_1_2_11_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lanepe.2021.100164"},{"key":"e_1_2_11_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2021.04.007"},{"key":"e_1_2_11_48_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-03398-2"},{"key":"e_1_2_11_49_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.3001384"},{"key":"e_1_2_11_50_1","doi-asserted-by":"crossref","unstructured":"WangE ChakrabortyAKDesign of immunogens for eliciting antibody responses that may protect against SARS\u2010CoV\u20102 variants. bioRxiv.2022.","DOI":"10.1101\/2022.01.24.477469"}],"container-title":["Journal of Medical Virology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jmv.27881","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jmv.27881","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jmv.27881","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,9,25]],"date-time":"2024-09-25T18:39:37Z","timestamp":1727289577000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jmv.27881"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,6]]},"references-count":49,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2022,9]]}},"alternative-id":["10.1002\/jmv.27881"],"URL":"https:\/\/doi.org\/10.1002\/jmv.27881","archive":["Portico"],"relation":{},"ISSN":["0146-6615","1096-9071"],"issn-type":[{"value":"0146-6615","type":"print"},{"value":"1096-9071","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,6]]},"assertion":[{"value":"2022-03-20","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-05-23","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-06-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}