Vaccine against Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) 

Damaged Lungs (Yellow) in a COVID-19 Patient in 3D Based on Computerized Tomography.  Source: Science

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.

Coronavirus (SARS-CoV-2 is shown in orange (scanning electron micrograph image).  SARS-CoV2 causes COVID-19 (isolated from a patient in the U.S., emerging from the surface of cells in green cultured in the lab. Image captured and colorized at NIAID’s Rocky Mountain Laboratories (RML) in Hamilton, Montana). Source: NIAID

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.

Refer to:

• 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