{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,12]],"date-time":"2025-12-12T11:31:27Z","timestamp":1765539087497,"version":"3.48.0"},"reference-count":20,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,12,5]],"date-time":"2025-12-05T00:00:00Z","timestamp":1764892800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"CanSino Biologics, Inc."}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>Background\/Objectives: Varicella-zoster virus (VZV) causes herpes zoster (HZ\/shingles), particularly in older adults with weakened cell-mediated immunity (CMI), which is essential for controlling VZV reactivation and reducing HZ severity. Currently vaccines, like recombinant subunit or live-attenuated vaccine, showed shortcomings in eliciting CD8+ T-cell responses. Addressing this, we utilized the novel replication-defective chimpanzee adenovirus vector ChAdOx1 to construct the ChAdOx1-VZV (CVE) vaccine, using full-length glycoprotein E (gE) as antigen. This study evaluated the immunogenicity of a heterologous intramuscular (IM) prime\/intranasal (IN) boost regimen with the aim of developing a novel VZV vaccine candidate. Methods: BALB\/c mice were immunized with CVE using homologous or heterologous prime-boost regimens via IM or IN. And cynomolgus macaques were immunized intramuscularly with three doses of CVE. Cellular responses were assessed by intracellular cytokine staining (ICS) and IFN-\u03b3 ELISpot using splenocytes and PBMCs. Humoral responses were evaluated by serum gE-IgG ELISA and bone-marrow LLPC ELISpot. Memory subsets and tissue-resident T cells were analyzed by flow cytometry. Results: Heterologous IM prime\/IN boost CVE regimen markedly enhanced both cellular and humoral responses, especially CD8+ T-cell responses. The induced LLPC and memory T cell responses indicate the potential for long-term protection against herpes zoster. In cynomolgus macaques, CVE induced robust serum gE-specific IgG responses and strong IFN-\u03b3 secreting T-cell activity, supporting the immunogenicity of CVE in a genetically distinct primate model and enhancing its clinical translational potential. Conclusions: CVE induces potent cellular and humoral immunogenicity, with IM prime\/IN boost vaccination. Cross species immunogenicity observed in nonhuman primates further strengthens the translational relevance of this platform. These findings support CVE as a promising herpes zoster vaccine candidate and provide a rationale for continued evaluation in human-relevant systems.<\/jats:p>","DOI":"10.3390\/vaccines13121226","type":"journal-article","created":{"date-parts":[[2025,12,5]],"date-time":"2025-12-05T10:50:38Z","timestamp":1764931838000},"page":"1226","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Heterologous Prime-Boost with ChAdOx1-VZV Establishes Dual-Layer Immunogenicity Conferring Protective Potential Against Herpes Zoster"],"prefix":"10.3390","volume":"13","author":[{"given":"Jiayu","family":"Zhao","sequence":"first","affiliation":[{"name":"CanSino Biologics Research Center, Tianjin 300457, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juan","family":"Shao","sequence":"additional","affiliation":[{"name":"CanSino Biologics Research Center, Tianjin 300457, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiuwen","family":"Sui","sequence":"additional","affiliation":[{"name":"CanSino Biologics Research Center, Tianjin 300457, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Menghan","family":"Wei","sequence":"additional","affiliation":[{"name":"CanSino Biologics Research Center, Tianjin 300457, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xinjian","family":"Ma","sequence":"additional","affiliation":[{"name":"CanSino Biologics Research Center, Tianjin 300457, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhijun","family":"Xu","sequence":"additional","affiliation":[{"name":"CanSino Biologics Research Center, Tianjin 300457, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4197-0065","authenticated-orcid":false,"given":"Tao","family":"Zhu","sequence":"additional","affiliation":[{"name":"CanSino Biologics Research Center, Tianjin 300457, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1111\/cei.12809","article-title":"Herpes Zoster and the Search for an Effective Vaccine","volume":"187","author":"Arnold","year":"2016","journal-title":"Clin. Exp. Immunol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"861","DOI":"10.2146\/ajhp170399","article-title":"Herpes Zoster Subunit Vaccine for the Prevention of Herpes Zoster","volume":"75","author":"Symoniak","year":"2018","journal-title":"Am. J. Health-Syst. Pharm."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2087","DOI":"10.1056\/NEJMoa1501184","article-title":"Efficacy of an Adjuvanted Herpes Zoster Subunit Vaccine in Older Adults","volume":"372","author":"Lal","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"91","DOI":"10.15585\/mmwr.mm6804a4","article-title":"Postlicensure Safety Surveillance of Recombinant Zoster Vaccine (Shingrix)\u2014United States, October 2017\u2013June 2018","volume":"68","author":"Hesse","year":"2019","journal-title":"MMWR Morb. Mortal. Wkly. Rep."},{"key":"ref_5","first-page":"e59086","article-title":"A Case Report of Shingles Vaccine as a Cause of Third Nerve Palsy: A Novel Etiology","volume":"16","author":"Sanchez","year":"2024","journal-title":"Cureus"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"100962","DOI":"10.1016\/j.ajoc.2020.100962","article-title":"Acute Retinal Necrosis Following Recombinant Subunit Varicella-Zoster Virus Vaccine","volume":"20","author":"Chen","year":"2020","journal-title":"Am. J. Ophthalmol. Case Rep."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Anastassopoulou, C., Ferous, S., Medi\u0107, S., Siafakas, N., Boufidou, F., Gioula, G., and Tsakris, A. (2024). Vaccines for the Elderly and Vaccination Programs in Europe and the United States. Vaccines, 12.","DOI":"10.3390\/vaccines12060566"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2704","DOI":"10.1128\/JVI.03445-13","article-title":"Analysis of T Cell Responses during Active Varicella-Zoster Virus Reactivation in Human Ganglia","volume":"88","author":"Steain","year":"2014","journal-title":"J. Virol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"6776","DOI":"10.1016\/j.vaccine.2019.09.031","article-title":"VZV-Specific Cell-Mediated Immunity, but Not Humoral Immunity, Correlates Inversely with the Incidence of Herpes Zoster and the Severity of Skin Symptoms and Zoster-Associated Pain: The SHEZ Study","volume":"37","author":"Asada","year":"2019","journal-title":"Vaccine"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1336","DOI":"10.1086\/379048","article-title":"Decline in Varicella-Zoster Virus (VZV)\u2013Specific Cell-Mediated Immunity with Increasing Age and Boosting with a High-Dose VZV Vaccine","volume":"188","author":"Levin","year":"2003","journal-title":"J. Infect. Dis."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e125","DOI":"10.1093\/cid\/ciz1090","article-title":"Herpes Zoster Risk in Immunocompromised Adults in the United States: A Systematic Review","volume":"71","author":"McKay","year":"2020","journal-title":"Clin. Infect. Dis."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2092","DOI":"10.1080\/21645515.2016.1154247","article-title":"Comparative Preclinical Evaluation of AS01 versus Other Adjuvant Systems in a Candidate Herpes Zoster Glycoprotein E Subunit Vaccine","volume":"12","author":"Fochesato","year":"2016","journal-title":"Hum. Vacc. Immunother."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1654","DOI":"10.1016\/S1473-3099(21)00396-0","article-title":"Safety, Tolerability, and Immunogenicity of an Aerosolised Adenovirus Type-5 Vector-Based COVID-19 Vaccine (Ad5-nCoV) in Adults: Preliminary Report of an Open-Label and Randomised Phase 1 Clinical Trial","volume":"21","author":"Wu","year":"2021","journal-title":"Lancet Infect. Dis."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1016\/S2213-2600(22)00087-X","article-title":"Safety and Immunogenicity of Heterologous Boost Immunisation with an Orally Administered Aerosolised Ad5-nCoV after Two-Dose Priming with an Inactivated SARS-CoV-2 Vaccine in Chinese Adults: A Randomised, Open-Label, Single-Centre Trial","volume":"10","author":"Li","year":"2022","journal-title":"Lancet Respir. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1781","DOI":"10.1038\/s41467-017-01901-w","article-title":"Plasma Cell Survival in the Absence of B Cell Memory","volume":"8","author":"Hammarlund","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"4802","DOI":"10.1073\/pnas.0800555105","article-title":"Maintenance of the Plasma Cell Pool Is Independent of Memory B Cells","volume":"105","author":"Ahuja","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2736","DOI":"10.1002\/jmv.27538","article-title":"The Global Disease Burden of Varicella-zoster Virus Infection from 1990 to 2019","volume":"94","author":"Huang","year":"2022","journal-title":"J. Med. Virol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1167","DOI":"10.1038\/s41467-018-03569-2","article-title":"A Spliced Latency-Associated VZV Transcript Maps Antisense to the Viral Transactivator Gene 61","volume":"9","author":"Depledge","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"S111","DOI":"10.1002\/jmv.10364","article-title":"Varicella in Americans from NHANES III: Implications for Control through Routine Immunization","volume":"70","author":"Kilgore","year":"2003","journal-title":"J. Med. Virol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"4757","DOI":"10.1038\/s41467-023-40489-2","article-title":"Safety and Immunogenicity of Ad5-nCoV Immunization after Three-Dose Priming with Inactivated SARS-CoV-2 Vaccine in Chinese Adults","volume":"14","author":"Zhang","year":"2023","journal-title":"Nat. Commun."}],"container-title":["Vaccines"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-393X\/13\/12\/1226\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,12]],"date-time":"2025-12-12T11:27:55Z","timestamp":1765538875000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-393X\/13\/12\/1226"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,5]]},"references-count":20,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["vaccines13121226"],"URL":"https:\/\/doi.org\/10.3390\/vaccines13121226","relation":{},"ISSN":["2076-393X"],"issn-type":[{"type":"electronic","value":"2076-393X"}],"subject":[],"published":{"date-parts":[[2025,12,5]]}}}