ChAdOx1

ChAdOx1 is an adenoviral vector for vaccines that was 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 chimpanzee 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] Serotype Y25 belongs to the species Human mastadenovirus E of genus Mastadenovirus.

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 RD, Coughlan L, Berthoud TK, Dicks MD, Hill AV, Lambe T, Gilbert SC (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. PMC 3944330. PMID 24374965.
  2. Dicks MD, Spencer AJ, Edwards NJ, Wadell G, Bojang K, Gilbert SC, et al. (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. Bibcode:2012PLoSO...740385D. doi:10.1371/journal.pone.0040385. PMC 3396660. PMID 22808149.
  3. Morris SJ, Sebastian S, Spencer AJ, Gilbert SC (September 2016). "Simian adenoviruses as vaccine vectors". Future Virology. 11 (9): 649–659. doi:10.2217/fvl-2016-0070. PMC 5842362. PMID 29527232.
  4. Munster VJ, Wells D, Lambe T, Wright D, Fischer RJ, Bushmaker T, et al. (December 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): 28. doi:10.1038/s41541-017-0029-1. PMC 5643297. PMID 29263883.
  5. "New MERS Coronavirus vaccine clinical trial starts in Saudi Arabia". 20 December 2019.
  6. van Doremalen N, Lambe T, Sebastian S, Bushmaker T, Fischer R, Feldmann F, et al. (June 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. PMC 6581282. PMID 31170144.
  7. Warimwe GM, Gesharisha J, Carr BV, Otieno S, Otingah K, Wright D, et al. (February 2016). "Chimpanzee Adenovirus Vaccine Provides Multispecies Protection against Rift Valley Fever". Scientific Reports. 6 (1): 20617. Bibcode:2016NatSR...620617W. doi:10.1038/srep20617. PMC 4742904. PMID 26847478.
  8. "Helen McShane". Nuffield Department of Medicine. Archived from the original on 26 August 2020. Retrieved 5 December 2020.
  9. Clinical trial number NCT03203421 for "A Safety and Efficacy Study of ChAdOx1 LS2 and MVA LS2" at ClinicalTrials.gov
  10. López-Camacho C, Dowall S, Graham V, Findlay-Wilson S, Rayner E, Kim YC, et al. (14 January 2019). "A Zika vaccine based on chimpanzee adenovirus ChAdOx1 elicits lineage-transcending sterile immunity and prevents colonisation of brain and ovaries". bioRxiv 10.1101/514877.
  11. López-Camacho C, Kim YC, Blight J, Lazaro Moreli M, Montoya-Diaz E, Huiskonen JT, et al. (April 2019). "Assessment of Immunogenicity and Neutralisation Efficacy of Viral-Vectored Vaccines Against Chikungunya Virus". Viruses. 11 (4): 322. doi:10.3390/v11040322. PMC 6521086. PMID 30987160.
  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.
  15. Lane R (April 2020). "Sarah Gilbert: carving a path towards a COVID-19 vaccine". 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 I (19 March 2020). "Trials to begin on Covid-19 vaccine in UK next month". The Guardian.
  18. Robson S (20 March 2020). "British scientists hope to start coronavirus vaccine trials next month". manchestereveningnews.co.uk. Retrieved 27 March 2020.
  19. Devlin H (27 March 2020). "UK scientists enrol volunteers for coronavirus vaccine trial". The Guardian.
  20. Folegatti PM, Ewer KJ, Aley PK, Angus B, Becker S, Belij-Rammerstorfer S, et al. (August 2020). "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". Lancet. 396 (10249): 467–478. doi:10.1016/S0140-6736(20)31604-4. hdl:10044/1/81821. PMC 7445431. PMID 32702298. S2CID 220651577.
  21. Gallagher J, Triggle N (30 December 2020). "Covid-19: Oxford-AstraZeneca vaccine approved for use in UK". BBC News.

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