{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T12:46:20Z","timestamp":1787921180521,"version":"build-2784847793"},"reference-count":45,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,3,15]],"date-time":"2023-03-15T00:00:00Z","timestamp":1678838400000},"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. Immunol."],"abstract":"<jats:p>The ongoing evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 or 2019-nCoV) variants has been associated with the transmission and pathogenicity of COVID-19. Therefore, exploring the optimal immunisation strategy to improve the broad-spectrum cross-protection ability of COVID-19 vaccines is of great significance. Herein, we assessed different heterologous prime-boost strategies with chimpanzee adenovirus vector-based COVID-19 vaccines plus Wuhan-Hu-1 (WH-1) strain (AdW) and Beta variant (AdB) and mRNA-based COVID-19 vaccines plus WH-1 strain (ARW) and Omicron (B.1.1.529) variant (ARO) in 6-week-old female BALB\/c mice. AdW and AdB were administered intramuscularly or intranasally, while ARW and ARO were administered intramuscularly. Intranasal or intramuscular vaccination with AdB followed by ARO booster exhibited the highest levels of cross-reactive IgG, pseudovirus-neutralising antibody (PNAb) responses, and angiotensin-converting enzyme-2 (ACE2)-binding inhibition rates against different 2019-nCoV variants among all vaccination groups. Moreover, intranasal AdB vaccination followed by ARO induced higher levels of IgA and neutralising antibody responses against live 2019-nCoV than intramuscular AdB vaccination followed by ARO. A single dose of AdB administered intranasally or intramuscularly induced broader cross-NAb responses than AdW. Th1-biased cellular immune response was induced in all vaccination groups. Intramuscular vaccination-only groups exhibited higher levels of Th1 cytokines than intranasal vaccination-only and intranasal vaccination-containing groups. However, no obvious differences were found in the levels of Th2 cytokines between the control and all vaccination groups. Our findings provide a basis for exploring vaccination strategies against different 2019-nCoV variants to achieve high broad-spectrum immune efficacy.<\/jats:p>","DOI":"10.3389\/fimmu.2023.1142394","type":"journal-article","created":{"date-parts":[[2023,3,15]],"date-time":"2023-03-15T04:49:12Z","timestamp":1678855752000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["Heterologous prime-boost immunisation with mRNA- and AdC68-based 2019-nCoV variant vaccines induces broad-spectrum immune responses in mice"],"prefix":"10.3389","volume":"14","author":[{"given":"Xingxing","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingjing","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjuan","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qinhua","family":"Peng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miao","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhifang","family":"Ying","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zelun","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyu","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohong","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danhua","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lihong","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shouchun","family":"Cao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanqiu","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leitai","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongshan","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunpeng","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guangzhi","family":"Yue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Suo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianhui","family":"Nie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weijin","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuhua","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,3,15]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2739-1","article-title":"The coding capacity of SARS-CoV-2","volume":"589","author":"Finkel","year":"2021","journal-title":"Nature"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1002\/mco2.110","article-title":"SARS-CoV-2 omicron variant: Characteristics and prevention","volume":"2","author":"He","year":"2021","journal-title":"MedComm"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1515\/dx-2021-0149","article-title":"Updated picture of SARS-CoV-2 variants and mutations","volume":"9","author":"Lippi","year":"2021","journal-title":"Diagn (Berl)"},{"key":"B4","article-title":"Emerging variants of SARS-CoV-2 and novel therapeutics against coronavirus (COVID-19)","volume-title":"StatPearls","author":"Aleem","year":"2022"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1002\/jmv.27588","article-title":"Omicron variant of SARS-CoV-2: Genomics, transmissibility, and responses to current COVID-19 vaccines","volume":"94","author":"Araf","year":"2022","journal-title":"J Med Virol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1002\/jmv.27643","article-title":"The emergence and epidemic characteristics of the highly mutated SARS-CoV-2 omicron variant","volume":"94","author":"Tian","year":"2022","journal-title":"J Med Virol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-04387-1","article-title":"Omicron extensively but incompletely escapes pfizer BNT162b2 neutralization","volume":"602","author":"Cele","year":"2022","journal-title":"Nature"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2119451","article-title":"Covid-19 vaccine effectiveness against the omicron (B.1.1.529) variant","volume":"386","author":"Andrews","year":"2022","journal-title":"N Engl J Med"},{"key":"B9","doi-asserted-by":"publisher","first-page":"257","DOI":"10.1038\/s41392-022-01065-0","article-title":"Comparative characterization of antibody responses induced by Ad5-vectored spike proteins of emerging SARS-CoV-2 VOCs","volume":"7","author":"Wang","year":"2022","journal-title":"Signal Transduct Target Ther"},{"key":"B10","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1186\/s12929-022-00830-1","article-title":"A booster dose of delta \u00d7 omicron hybrid mRNA vaccine produced broadly neutralizing antibody against omicron and other SARS-CoV-2 variants","volume":"29","author":"Lee","year":"2022","journal-title":"J BioMed Sci"},{"key":"B11","doi-asserted-by":"publisher","first-page":"3250","DOI":"10.1038\/s41467-022-30878-4","article-title":"Omicron-specific mRNA vaccination alone and as a heterologous booster against SARS-CoV-2","volume":"13","author":"Fang","year":"2022","journal-title":"Nat Commun"},{"key":"B12","doi-asserted-by":"publisher","first-page":"1728","DOI":"10.1016\/j.cell.2022.03.044","article-title":"Circular RNA vaccines against SARS-CoV-2 and emerging variants","volume":"185","author":"Qu","year":"2022","journal-title":"Cell"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1101\/2022.04.07.487347","article-title":"Plant-produced RBD and cocktail-based vaccine candidates are highly effective against SARS-CoV-2, independently of its emerging variants","author":"Mamedov","year":"2022","journal-title":"bioRxiv"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-021-01677-z","article-title":"Heterologous AD5-nCOV plus CoronaVac versus homologous CoronaVac vaccination: A randomized phase 4 trial","volume":"28","author":"Li","year":"2022","journal-title":"Nat Med"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(21)00420-5","article-title":"Heterologous prime\u2013boost vaccination with ChAdOx1 nCoV-19 and BNT162b2","volume":"21","author":"Tenbusch","year":"2021","journal-title":"Lancet Infect Dis"},{"key":"B16","doi-asserted-by":"publisher","first-page":"419","DOI":"10.1038\/s41392-021-00843-6","article-title":"Heterologous prime-boost with AdC68- and mRNA-based COVID-19 vaccines elicit potent immune responses in mice","volume":"6","author":"Li","year":"2021","journal-title":"Signal Transduct Target Ther"},{"key":"B17","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1016\/j.imlet.2009.03.013","article-title":"Specific antibody activity, glycan heterogeneity and polyreactivity contribute to the protective activity of s-IgA at mucosal surfaces","volume":"124","author":"Mestecky","year":"2009","journal-title":"Immunol Lett"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1101\/2020.09.09.288555","article-title":"Enhanced SARS-CoV-2 neutralization by secretory IgA in vitro","author":"Wang","year":"2020","journal-title":"bioRxiv"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00408-20","article-title":"Potential role of nonneutralizing IgA antibodies in cross-protective immunity against influenza a viruses of multiple hemagglutinin subtypes","volume":"94","author":"Okuya","year":"2020","journal-title":"J Virol"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1038\/s41422-022-00626-w","article-title":"Rapid development of an updated mRNA vaccine against the SARS-CoV-2 omicron variant","volume":"32","author":"Zhang","year":"2022","journal-title":"Cell Res"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1038\/s41596-020-0394-5","article-title":"Quantification of SARS-CoV-2 neutralizing antibody by a pseudotyped virus-based assay","volume":"15","author":"Nie","year":"2020","journal-title":"Nat Protoc"},{"key":"B22","doi-asserted-by":"publisher","first-page":"2384","DOI":"10.1016\/j.cell.2021.03.036","article-title":"SARS-CoV-2 variants B.1.351 and P.1 escape from neutralizing antibodies","volume":"184","author":"Hoffmann","year":"2021","journal-title":"Cell"},{"key":"B23","doi-asserted-by":"publisher","first-page":"467","DOI":"10.1016\/j.cell.2021.12.046","article-title":"SARS-CoV-2 omicron-B.1.1.529 leads to widespread escape from neutralizing antibody responses","volume":"185","author":"Dejnirattisai","year":"2022","journal-title":"Cell"},{"key":"B24","doi-asserted-by":"publisher","first-page":"2372","DOI":"10.1016\/j.cell.2021.03.013","article-title":"Multiple SARS-CoV-2 variants escape neutralization by vaccine-induced humoral immunity","volume":"184","author":"Garcia-Beltran","year":"2021","journal-title":"Cell"},{"key":"B25","doi-asserted-by":"publisher","first-page":"5736","DOI":"10.1038\/s41467-022-33378-7","article-title":"Effectiveness of COVID-19 vaccines against omicron and delta hospitalisation, a test negative case-control study","volume":"13","author":"Stowe","year":"2022","journal-title":"Nat Commun"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMc2104974","article-title":"National study group for COVID-19 vaccination. effectiveness of the BNT162b2 covid-19 vaccine against the B.1.1.7 and B.1.351 variants","volume":"385","author":"Abu-Raddad","year":"2021","journal-title":"N Engl J Med"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2103055","article-title":"Efficacy of NVX-CoV2373 covid-19 vaccine against the B.1.351 variant","volume":"384","author":"Shinde","year":"2021","journal-title":"N Engl J Med"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1186\/s12929-022-00830-1","article-title":"Omicron-specific mRNA vaccine induced potent neutralizing antibody against omicron but not other SARS-CoV-2 variants","author":"Lee","year":"2022","journal-title":"bioRxiv"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.898520","article-title":"The cross-protective immunity landscape among different SARS-CoV-2 variant RBDs","volume":"13","author":"Sun","year":"2022","journal-title":"Front Immunol"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1080\/22221751.2022.2081616","article-title":"mRNA based vaccines provide broad protection against different SARS-CoV-2 variants of concern","volume":"11","author":"Wang","year":"2022","journal-title":"Emerg Microbes Infect"},{"key":"B31","doi-asserted-by":"publisher","first-page":"1699","DOI":"10.1038\/s41467-022-29219-2","article-title":"Protein-based SARS-CoV-2 spike vaccine booster increases cross-neutralization against SARS-CoV-2 variants of concern in non-human primates","volume":"13","author":"Pavot","year":"2022","journal-title":"Nat Commun"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2020.110559","article-title":"Targeting SARS-CoV2 spike protein receptor binding domain by therapeutic antibodies","volume":"130","author":"Hussain","year":"2020","journal-title":"BioMed Pharmacother"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.abk3445","article-title":"Predicting the mutational drivers of future SARS-CoV-2 variants of concern","volume":"14","author":"Maher","year":"2022","journal-title":"Sci Transl Med"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1016\/j.csbj.2022.06.043","article-title":"Severe acute respiratory syndrome coronavirus 2 variants\u2013possibility of universal vaccine design: A review","volume":"20","author":"Yoon","year":"2022","journal-title":"Comput Struct Biotechnol J"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1101\/2022.05.10.491301","article-title":"Preclinical evaluation of RQ3013, a broad-spectrum mRNA vaccine against SARS-CoV-2 variants","author":"Tan","year":"2022","journal-title":"bioRxiv"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1155\/2020\/2032057","article-title":"The effects of secretory IgA in the mucosal immune system","volume":"2020","author":"Li","year":"2020","journal-title":"BioMed Res Int"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.abd2223","article-title":"IgA dominates the early neutralizing antibody response to SARS-CoV-2","volume":"13","author":"Sterlin","year":"2021","journal-title":"Sci Transl Med"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1097\/QCO.0000000000000724","article-title":"Mucosal immunity to severe acute respiratory syndrome coronavirus 2 infection","volume":"34","author":"Fr\u00f6berg","year":"2021","journal-title":"Curr Opin Infect Dis"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2021.655896","article-title":"IgA antibodies and IgA deficiency in SARS-CoV-2 infection","volume":"11","author":"Quinti","year":"2021","journal-title":"Front Cell Infect Microbiol"},{"key":"B40","doi-asserted-by":"publisher","first-page":"eabf1555","DOI":"10.1126\/scitranslmed.abf1555","article-title":"Enhanced SARS-CoV-2 neutralization by dimeric IgA","volume":"13","author":"Wang","year":"2021","journal-title":"Sci Transl Med"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-021-01122-w","article-title":"The T cell immune response against SARS-CoV-2","volume":"23","author":"Moss","year":"2022","journal-title":"Nat Immunol"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2814-7","article-title":"COVID-19 vaccine BNT162b1 elicits human antibody and TH1 T cell responses","volume":"586","author":"Sahin","year":"2020","journal-title":"Nature"},{"key":"B43","doi-asserted-by":"publisher","first-page":"847","DOI":"10.1016\/j.cell.2022.01.015","article-title":"SARS-CoV-2 vaccination induces immunological T cell memory able to cross-recognize variants from alpha to omicron","volume":"185","author":"Tarke","year":"2022","journal-title":"Cell"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1080\/22221751.2022.2097479","article-title":"Combining intramuscular and intranasal homologous prime-boost with a chimpanzee adenovirus-based COVID-19 vaccine elicits potent humoral and cellular immune responses in mice","volume":"11","author":"Li","year":"2022","journal-title":"Emerg Microbes Infect"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1128\/CVI.00131-10","article-title":"Correlates of protection induced by vaccination","volume":"17","author":"Plotkin","year":"2010","journal-title":"Clin Vaccine Immunol"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2023.1142394\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,3,15]],"date-time":"2023-03-15T04:49:15Z","timestamp":1678855755000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2023.1142394\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3,15]]},"references-count":45,"alternative-id":["10.3389\/fimmu.2023.1142394"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2023.1142394","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,3,15]]},"article-number":"1142394"}}