Vaccine against Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2)
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is responsible for the COronVIirus Disease 2019 (COVID-19) pandemic.
The UK drug manufacturer AstraZeneca has partnered with the University of Oxford to develop the adenovirus-vectored vaccine against SARS-CoV-2.
An investigational adenovirus-vectored vaccine (ChAdOx1 nCoV-19: AZD1222) against SARS-CoV-2 is currently being tested in phases 2/3 clinical trials.
In animal studies in rhesus macaques, a single vaccination with ChAdOx1 nCoV-19 was effective:
- in preventing damage to the lungs upon high dose challenge with the virus (SARS-CoV-2);
- in preventing virus replication in the lower respiratory tract; and
- inducing a humoral and cellular immune response.
For animal studies, refer to bioRxiv preprint doi: https://doi.org/10.1101/2020.05.13.093195 entitled “ChAdOx1 nCoV-19 vaccination prevents SARS-CoV-2 1 pneumonia in rhesus macaques”, which is based on a US government work.
In rhesus macaques (a non-human primate model), twenty-eight (28) days before inoculation with SARS-CoV-2, 6 animals were vaccinated with 2.5 x 1010 ChAdOx1 nCoV-19 virus particles each intramuscularly (in currently clinical trials in human, half of the dose is administered).
In human clinical trials (phases 2/3), it is currently being tested in 10260 healthy UK volunteers.
The vaccine (ChAdOx1 nCoV-19: AZD1222) is tested to assess the following:
- Primary safety endpoint is to assess the safety of the candidate vaccine ChAdOx1 nCoV-19 in adults and children.
- Primary efficacy endpoint is to assess the efficacy of the candidate ChAdOx1 nCoV-19 against COVID-19 in adults aged 18 years and older.
- Phases 1/2: ClinicalTrials.gov Identifier: NCT04324606 (in UK healthy adult volunteers aged 18-55 years)
- Phases 1/2: ClinicalTrials.gov Identifier: NCT04444674 (in adults aged 18-65 years living with and without HIV in South Africa)
- Phases 2/3: ClinicalTrials.gov Identifier: NCT04400838
- This phase 2/3 Study Is to Determine the Efficacy, Safety and Immunogenicity of the Candidate Coronavirus Disease (COVID-19) Vaccine ChAdOx1 nCoV-19
Vaccine Design: ChAdOx1 nCoV-19
A simian adenoviral vector (ChAdOx1) was designed to encode a codon-optimised full-length spike protein of SARS-CoV-2* with a human tissue plasminogen activator (tPA) leader sequence (named ChAdOx1 nCoV-19 or AZD1222). The fusion is in the order N-terminus – tPA – spike protein – C-terminus. This design was shown to have surprising benefits (e.g., the absence of hypersensitivity type reactions after immunization).
*:NCBI Reference Sequence: YP_009724390.1
A major benefit of this vaccine is the induction of immune response after only a single vaccine administration. The optional incorporation of a leader sequence/secretory sequence such as the tissue plasminogen activator (tPA) amino acid sequence fused to the N-terminus of the SARS-CoV-2 spike protein antigen, which creates a triple combination (ChAdOxi + tPA + SARS-CoV-2 spike protein) is intended to deliver enhanced immunogenicity (protective immunity).
Last Updated: 2020-06-29
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