ChAdOx1

ChAdOx1 is a adenoviral vaccine vector developed by the Jenner Institute, University of Oxford. The vector is a chimpanzee adenovirus modified to avoid its replication.

For the COVID-19 vaccine that uses ChAdOx1 as a vector, see Oxford–AstraZeneca COVID-19 vaccine.

Adenoviruses are effective vectors for inducing and boosting cellular immunity to encoded recombinant antigens. However, the widespread seroprevalence of neutralizing antibodies to common human adenovirus serotypes limits their use. Simian adenoviruses do not suffer from the same disadvantages. Therefore, investigators have tested new vaccines using the chimp adenovirus ChAdOx1 as a vector. For example, a vaccine for influenza infection was designed using the vector expressing influenza antigens, nucleoprotein (NP), and matrix protein 1 (M1), creating a vaccine candidate named ChAdOx1 NP+M1.[1]

Virology

ChAdOx1 has been derived from a simian adenovirus (ChAd) serotype Y25 engineered by λ red recombination to exchange the native E4 orf4, orf6 and orf6/7 genes for those from human adenovirus HAdV-C5.[2][3]

Clinical trials

It has been demonstrated that the adenoviridae vector ChAdOx1 can be used to make vaccinations that are protective against Middle East Respiratory Syndrome (MERS) in mice and able to induce immune response against MERS in humans.[4][5]

The vector was also used to create a vaccine against Nipah which was effective in hamsters (but never proven in humans),[6] in addition to a potential vaccine for Rift Valley Fever that was protective in sheep, goats, and cattle (but not proven in humans).[7]

The adenovirus expressing the antigen 85A (ChAdOx1 85A), is used as vector for a tuberculosis vaccine candidate.[8]

In 2017, the ChAdOx1 vector was used in a trial for a vaccine candidate against human malaria infection. The researchers studied two candidate vaccines ChAdOx1 LS2 along with MVA LS2. The former, encoding a malaria liver-stage dual antigen LS2 (LSA1 and LSAP2) fused with the transmembrane domain from shark invariant chain. And the latter, a Modified Vaccinia Ankara (MVA) vector encoding the LS2 fused to the C-terminal end of the leader sequence of tPA. The trial reached the phase I/IIa.[9]

There are also investigation lines that use the vector for vaccines against the Zika virus (ChAdOx1 ZIKV)[10] and the Chikungunya virus (ChAdOx1 sCHIKV).[11]

The ChAdOx1 vector has been used as a platform for a vaccine against coronavirus disease since the beginning of the COVID-19 pandemic.[12][13][14][15] Sarah Gilbert leads the work on this vaccine candidate alongside Andrew Pollard, Teresa Lambe, Sandy Douglas, Catherine Green and Adrian Hill.[16] The COVID-19 vaccine, known now as ChAdOx1 nCoV-19 or AZD1222, makes use of this vector, which stimulates an immune response against the coronavirus spike protein.[12][13] Animal studies began in March 2020, and recruitment of 510 human participants for a phase I/II trial began on 27 March.,[17][18][19] and the results were presented in October.[20] On 30 December 2020 the vaccine was approved for use[21] in the UK's vaccination programme.

References
  1. Antrobus, Richard D.; Coughlan, Lynda; Berthoud, Tamara K.; Dicks, Matthew D.; Hill, Adrian VS; Lambe, Teresa; Gilbert, Sarah C. (1 March 2014). "Clinical Assessment of a Novel Recombinant Simian Adenovirus ChAdOx1 as a Vectored Vaccine Expressing Conserved Influenza A Antigens". Molecular Therapy. 22 (3): 668–674. doi:10.1038/mt.2013.284. ISSN 1525-0016. PMID 24374965.
  2. Dicks, Matthew D. J.; Spencer, Alexandra J.; Edwards, Nick J.; Wadell, Göran; Bojang, Kalifa; Gilbert, Sarah C.; Hill, Adrian V. S.; Cottingham, Matthew G. (13 July 2012). "A Novel Chimpanzee Adenovirus Vector with Low Human Seroprevalence: Improved Systems for Vector Derivation and Comparative Immunogenicity". PLOS ONE. 7 (7): e40385. doi:10.1371/journal.pone.0040385. ISSN 1932-6203. PMC 3396660. PMID 22808149.
  3. Morris, Susan J; Sebastian, Sarah; Spencer, Alexandra J; Gilbert, Sarah C (1 September 2016). "Simian adenoviruses as vaccine vectors". Future Virology. 11 (9): 649–659. doi:10.2217/fvl-2016-0070. ISSN 1746-0794. PMC 5842362. PMID 29527232.
  4. Munster, Vincent J.; Wells, Daniel; Lambe, Teresa; Wright, Daniel; Fischer, Robert J.; Bushmaker, Trenton; Saturday, Greg; van Doremalen, Neeltje; Gilbert, Sarah C.; de Wit, Emmie; Warimwe, George M. (2017). "Protective efficacy of a novel simian adenovirus vaccine against lethal MERS-CoV challenge in a transgenic human DPP4 mouse model". npj Vaccines. 2 (1). doi:10.1038/s41541-017-0029-1. ISSN 2059-0105. PMC 5643297. PMID 29263883.
  5. "New MERS Coronavirus vaccine clinical trial starts in Saudi Arabia". 20 December 2019.
  6. Halstead, Scott B.; van Doremalen, Neeltje; Lambe, Teresa; Sebastian, Sarah; Bushmaker, Trenton; Fischer, Robert; Feldmann, Friederike; Haddock, Elaine; Letko, Michael; Avanzato, Victoria A.; Rissanen, Ilona; LaCasse, Rachel; Scott, Dana; Bowden, Thomas A.; Gilbert, Sarah; Munster, Vincent (2019). "A single-dose ChAdOx1-vectored vaccine provides complete protection against Nipah Bangladesh and Malaysia in Syrian golden hamsters". PLOS Neglected Tropical Diseases. 13 (6): e0007462. doi:10.1371/journal.pntd.0007462. ISSN 1935-2735. PMC 6581282. PMID 31170144.
  7. Warimwe, George M.; Gesharisha, Joseph; Carr, B. Veronica; Otieno, Simeon; Otingah, Kennedy; Wright, Danny; Charleston, Bryan; Okoth, Edward; Elena, Lopez-Gil; Lorenzo, Gema; Ayman, El-Behiry; Alharbi, Naif K.; Al-dubaib, Musaad A.; Brun, Alejandro; Gilbert, Sarah C.; Nene, Vishvanath; Hill, Adrian V. S. (2016). "Chimpanzee Adenovirus Vaccine Provides Multispecies Protection against Rift Valley Fever". Scientific Reports. 6 (1). doi:10.1038/srep20617. ISSN 2045-2322. PMC 4742904. PMID 26847478.
  8. "Helen McShane". Nuffield Department of Medicine. Retrieved 5 December 2020.
  9. "A Phase I/II Study to Assess the Safety, Immunogenicity and Protective Efficacy of Novel Malaria Vaccine Candidates ChAdOx1 LS2 and MVA LS2 in Healthy UK Adults". ClinicalTrials. University of Oxford. 12 June 2018. Retrieved 5 December 2020.
  10. López-Camacho, César; Dowall, Stuart; Graham, Victoria; Findlay-Wilson, Stephen; Rayner, Emma; Kim, Young Chan; Hewson, Roger; Reyes-Sandoval, Arturo (14 January 2019). "A Zika vaccine based on chimpanzee adenovirus ChAdOx1 elicits lineage-transcending sterile immunity and prevents colonisation of brain and ovaries". bioRxiv: 514877. doi:10.1101/514877.
  11. López-Camacho, César; Kim, Young Chan; Blight, Joshua; Lazaro Moreli, Marcos; Montoya-Diaz, Eduardo; T Huiskonen, Juha; Mareike Kümmerer, Beate; Reyes-Sandoval, Arturo (April 2019). "Assessment of Immunogenicity and Neutralisation Efficacy of Viral-Vectored Vaccines Against Chikungunya Virus". Viruses. 11 (4): 322. doi:10.3390/v11040322.
  12. "Two groups of UK scientists in race to develop coronavirus vaccine". Evening Standard. 7 February 2020. Retrieved 27 March 2020.
  13. "Vaccine trials among recipients of £20 million coronavirus research investment". GOV.UK. Retrieved 27 March 2020.
  14. "Oxford team to begin novel coronavirus vaccine research | University of Oxford". ox.ac.uk. Retrieved 27 March 2020.
  15. Lane, Richard (2020). "Sarah Gilbert: carving a path towards a COVID-19 vaccine". The Lancet. 395 (10232): 1247. doi:10.1016/S0140-6736(20)30796-0. PMC 7162644. PMID 32305089.
  16. "COVID-19 Vaccine Trials | COVID-19". covid19vaccinetrial.co.uk. Retrieved 11 April 2020.
  17. Sample, Ian (19 March 2020). "Trials to begin on Covid-19 vaccine in UK next month". The Guardian. ISSN 0261-3077. Retrieved 27 March 2020.
  18. Robson, Steve (20 March 2020). "British scientists hope to start coronavirus vaccine trials next month". manchestereveningnews.co.uk. Retrieved 27 March 2020.
  19. "UK scientists enrol volunteers for coronavirus vaccine trial". theguardian.com. The Guardian. 17 March 2020.
  20. "The Lancet | Safety and immunogenicity of the ChAdOx1 nCoV-19 vaccine against SARS-CoV-2: a preliminary report of a phase 1/2, single-blind, randomised controlled trial". www.thelancet.com. Retrieved 20 July 2020.
  21. "Covid-19: Oxford-AstraZeneca coronavirus vaccine approved for use in UK". BBC News. BBC. 30 December 2020. Retrieved 30 December 2020.

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