{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T14:07:09Z","timestamp":1793196429611,"version":"4.5.0"},"reference-count":29,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2021,10,28]],"date-time":"2021-10-28T00:00:00Z","timestamp":1635379200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MR\/P017339\/1"],"award-info":[{"award-number":["MR\/P017339\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["201477\/Z\/16\/Z"],"award-info":[{"award-number":["201477\/Z\/16\/Z"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>Adenovirus vectored vaccines have entered global use during the COVID-19 pandemic, and are in development for multiple other human and veterinary applications. An attraction of the technology is the suitability of the vaccines for storage at 2\u20138 \u00b0C for months. Widely used COVID-19 vaccine ChAdOx1 nCoV-19 (University of Oxford\/AstraZeneca) is based on a species E simian adenovirus. Species E simian serotypes have been used in a wide range of other development programs, but the stability of such vectors has not been extensively described in the peer-reviewed literature. Here, we explore the stability of two candidate vaccines based on two species E serotypes: a Rift Valley fever vaccine based upon the ChAdOx1 vector (Y25 serotype) used in ChAdOx1 nCoV-19, and a rabies vaccine based upon a ChAdOx2 vector (AdC68 serotype). We describe each vector\u2019s stability in liquid and lyophilised formulations using in vitro and in vivo potency measurements. Our data support the suitability of liquid formulations of these vectors for storage at 2\u20138 \u00b0C for up to 1 year, and potentially for nonrefrigerated storage for a brief period during last-leg distribution (perhaps 1\u20133 days at 20 \u00b0C\u2014the precise definition of acceptable last-leg storage conditions would require further product-specific data). Depending upon the level of inprocess potency loss that is economically acceptable, and the level of instorage loss that is compatible with maintenance of acceptable end-of-storage potency, a previously reported lyophilised formulation may enable longer term storage at 20 \u00b0C or storage for a number of days at 30 \u00b0C.<\/jats:p>","DOI":"10.3390\/vaccines9111249","type":"journal-article","created":{"date-parts":[[2021,10,28]],"date-time":"2021-10-28T23:52:35Z","timestamp":1635465155000},"page":"1249","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Stability of Chimpanzee Adenovirus Vectored Vaccines (ChAdOx1 and ChAdOx2) in Liquid and Lyophilised Formulations"],"prefix":"10.3390","volume":"9","author":[{"given":"Adam","family":"Berg","sequence":"first","affiliation":[{"name":"Wellcome Trust Centre for Human Genetics, Jenner Institute, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8114-1838","authenticated-orcid":false,"given":"Daniel","family":"Wright","sequence":"additional","affiliation":[{"name":"Wellcome Trust Centre for Human Genetics, Jenner Institute, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pawan","family":"Dulal","sequence":"additional","affiliation":[{"name":"Wellcome Trust Centre for Human Genetics, Jenner Institute, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Stedman","sequence":"additional","affiliation":[{"name":"The Pirbright Institute, Ash Road, Pirbright, Woking GU24 0NF, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sofiya","family":"Fedosyuk","sequence":"additional","affiliation":[{"name":"Wellcome Trust Centre for Human Genetics, Jenner Institute, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5433-0211","authenticated-orcid":false,"given":"Michael J.","family":"Francis","sequence":"additional","affiliation":[{"name":"BioVacc Consulting Ltd., The Red House, 10 Market Square, Amersham HP7 0DQ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bryan","family":"Charleston","sequence":"additional","affiliation":[{"name":"The Pirbright Institute, Ash Road, Pirbright, Woking GU24 0NF, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George M.","family":"Warimwe","sequence":"additional","affiliation":[{"name":"The Pirbright Institute, Ash Road, Pirbright, Woking GU24 0NF, UK"},{"name":"KEMRI-Wellcome Trust Research Programme, Kilifi P.O. Box 230-80108, Kenya"},{"name":"Centre for Tropical Medicine & Global Health, University of Oxford, Oxford OX3 7LG, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander D.","family":"Douglas","sequence":"additional","affiliation":[{"name":"Wellcome Trust Centre for Human Genetics, Jenner Institute, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,10,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.coi.2016.05.014","article-title":"Viral vectors as vaccine platforms: From immunogenicity to impact","volume":"41","author":"Ewer","year":"2016","journal-title":"Curr. Opin. Immunol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/S0140-6736(20)32661-1","article-title":"Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: An interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK","volume":"397","author":"Voysey","year":"2020","journal-title":"Lancet"},{"key":"ref_3","unstructured":"European Medicines Agency (2021, October 22). ZAbdeno European Public Assessment Report. 23 July 2020. Available online: https:\/\/www.ema.europa.eu\/en\/medicines\/human\/EPAR\/zabdeno."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"115ra2","DOI":"10.1126\/scitranslmed.3002925","article-title":"Vaccine vectors derived from a large collection of simian adenoviruses induce potent cellular immunity across multiple species","volume":"4","author":"Colloca","year":"2012","journal-title":"Sci. Transl. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2458","DOI":"10.1002\/jps.20157","article-title":"Development of stable liquid formulations for adenovirus-based vaccines","volume":"93","author":"Evans","year":"2004","journal-title":"J. Pharm. Sci."},{"key":"ref_6","unstructured":"Evans, R., Volkin, D., and Isopi, L. (2008). Adenovirus Formulations. (Patent 7456009B2), U.S."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2931","DOI":"10.1016\/j.vaccine.2014.02.033","article-title":"Use of adenovirus as a model system to illustrate a simple method using standard equipment and inexpensive excipients to remove live virus dependence on the cold-chain","volume":"32","author":"Stewart","year":"2014","journal-title":"Vaccine"},{"key":"ref_8","unstructured":"Jezek, J., and Buckler, A. (2020). Stable Aqueous Formulations of Adenovirus Vectors. (2968112-B2), EP Patent."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"818","DOI":"10.1016\/j.xphs.2019.10.063","article-title":"Algorithm-Based Liquid Formulation Development Including a DoE Concept Predicts Long-Term Viral Vector Stability","volume":"109","author":"Reinauer","year":"2020","journal-title":"J. Pharm. Sci."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"13520","DOI":"10.1038\/ncomms13520","article-title":"Additives for vaccine storage to improve thermal stability of adenoviruses from hours to months","volume":"7","author":"Pelliccia","year":"2016","journal-title":"Nat Commun."},{"key":"ref_11","unstructured":"(2021, October 22). Highlights of Prescribing Information: Adenovirus Type 4 and Type 7 Vaccine, Live, Oral Enteric Coated Tablets for Oral Administration, Available online: https:\/\/www.fda.gov\/media\/80211\/download."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1810","DOI":"10.1111\/jam.12654","article-title":"The influence of stabilizers and rates of freezing on preserving of structurally different animal viruses during lyophilization and subsequent storage","volume":"117","author":"Malenovska","year":"2014","journal-title":"J. Appl. Microbiol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1006\/mthe.2001.0411","article-title":"Development of novel formulations that enhance adenoviral-mediated gene expression in the lung in vitro and in vivo","volume":"4","author":"Croyle","year":"2001","journal-title":"Mol. Ther."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1281","DOI":"10.1038\/sj.gt.3301527","article-title":"Development of formulations that enhance physical stability of viral vectors for gene therapy","volume":"8","author":"Croyle","year":"2001","journal-title":"Gene Ther."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/j.ijpharm.2011.12.056","article-title":"Investigation on formulation and preparation of adenovirus encoding human endostatin lyophilized powders","volume":"427","author":"Chen","year":"2012","journal-title":"Int. J. Pharm."},{"key":"ref_16","unstructured":"Bourles, E., and Mathot, F. (2020). Pharmaceutical Composition Comprising an Adenoviral Vector. (US10722470B2), U.S. Patent."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2025","DOI":"10.1128\/JVI.01644-08","article-title":"DNA genome size affects the stability of the adenovirus virion","volume":"83","author":"Smith","year":"2009","journal-title":"J. Virol."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Dicks, M.D., Spencer, A.J., Edwards, N.J., Wadell, G., Bojang, K., Gilbert, S.C., Hill, A.V., and Cottingham, M.G. (2012). A novel chimpanzee adenovirus vector with low human seroprevalence: Improved systems for vector derivation and comparative immunogenicity. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0040385"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"649","DOI":"10.2217\/fvl-2016-0070","article-title":"Simian adenoviruses as vaccine vectors","volume":"11","author":"Morris","year":"2016","journal-title":"Future Virol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"772","DOI":"10.1093\/infdis\/jir850","article-title":"Clinical Assessment of a Recombinant Simian Adenovirus ChAd63: A Potent New Vaccine Vector","volume":"205","author":"Duncan","year":"2012","journal-title":"J. Infect. Dis."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Wang, C., Dulal, P., Zhou, X., Xiang, Z., Goharriz, H., Banyard, A., Green, N., Brunner, L., Ventura, R., and Collin, N. (2018). A simian-adenovirus-vectored rabies vaccine suitable for thermostabilisation and clinical development for low-cost single-dose pre-exposure prophylaxis. PLoS Negl. Trop. Dis., 12.","DOI":"10.1101\/408013"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2916","DOI":"10.1016\/j.vaccine.2017.04.026","article-title":"Spray dried human and chimpanzee adenoviral-vectored vaccines are thermally stable and immunogenic in vivo","volume":"35","author":"Afkhami","year":"2017","journal-title":"Vaccine"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1186\/1743-422X-10-349","article-title":"Immunogenicity and efficacy of a chimpanzee adenovirus-vectored Rift Valley fever vaccine in mice","volume":"10","author":"Warimwe","year":"2013","journal-title":"Virol. J."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"6951","DOI":"10.1016\/j.vaccine.2019.04.056","article-title":"Simian adenovirus vector production for early-phase clinical trials: A simple method applicable to multiple serotypes and using entirely disposable product-contact components","volume":"37","author":"Fedosyuk","year":"2019","journal-title":"Vaccine"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/0042-6822(68)90121-9","article-title":"The polypeptides of adenovirus. I. Evidence for multiple protein components in the virion and a comparison of types 2, 7A, and 12","volume":"36","author":"Maizel","year":"1968","journal-title":"Virology"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"101669","DOI":"10.1016\/j.isci.2020.101669","article-title":"Naturally Acquired Rift Valley Fever Virus Neutralizing Antibodies Predominantly Target the Gn Glycoprotein","volume":"23","author":"Wright","year":"2020","journal-title":"iScience"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1038\/s41541-019-0138-0","article-title":"Safety and efficacy of ChAdOx1 RVF vaccine against Rift Valley fever in pregnant sheep and goats","volume":"4","author":"Stedman","year":"2019","journal-title":"NPJ Vaccines"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"20617","DOI":"10.1038\/srep20617","article-title":"Chimpanzee Adenovirus Vaccine Provides Multispecies Protection against Rift Valley Fever","volume":"6","author":"Warimwe","year":"2016","journal-title":"Sci Rep."},{"key":"ref_29","unstructured":"(2021, October 18). Guidelines on the Stability Evaluation of Vaccines for Use under Extended Controlled Temperature Conditions, Annex 5, TRS No 999. Available online: https:\/\/www.who.int\/publications\/m\/item\/ectc-annex-5-trs-no-999."}],"container-title":["Vaccines"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-393X\/9\/11\/1249\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:21:51Z","timestamp":1760167311000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-393X\/9\/11\/1249"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10,28]]},"references-count":29,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2021,11]]}},"alternative-id":["vaccines9111249"],"URL":"https:\/\/doi.org\/10.3390\/vaccines9111249","relation":{},"ISSN":["2076-393X"],"issn-type":[{"value":"2076-393X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,10,28]]}}}