ChAdOx1

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

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.[1]

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.[citation needed
]

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

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

UK's vaccination programme
.

References

  1. ^
    PMID 24374965
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  2. PMID 22808149
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  3. PMID 29527232
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  4. PMID 29263883
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  5. ^ "New MERS Coronavirus vaccine clinical trial starts in Saudi Arabia". 20 December 2019. Archived from the original on 27 March 2020. Retrieved 5 December 2020.
  6. PMID 31170144
    .
  7. 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. bioRxiv 10.1101/514877
    .
  11. PMID 30987160
    .
  12. ^ a b "Two groups of UK scientists in race to develop coronavirus vaccine". Evening Standard. 7 February 2020. Retrieved 27 March 2020.
  13. ^ a b "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. PMID 32305089
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  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. 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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