University of Oxford/AstraZeneca COVID-19 vaccine

Name: COVID-19 Vaccine AstraZeneca (AZD1222 or ChAdOx1 nCoV-19)

Type: Viral vector vaccine (chimpanzee adenovirus vector)

Developer: Astra Zeneca

Recommended doses/interval: 2 doses, administered 12 weeks apart (noting a minimum interval of 4 weeks is acceptable)

Doses for Australia: 53.8 million doses, 3.8 million doses will be delivered to Australia in early 2021

Manufacturing: 50 million doses will be manufactured in Parkville, Australia in monthly batches by the local biotechnology company, CSL

Storage: Can be stored, transported and handled at standard refrigerator temperatures (2-8°C)

Background

The University of Oxford/AstraZeneca COVID-19 vaccine (ChAdOx1 nCoV-19) utilises a chimpanzee adenovirus (ChAdOx1) vector; which is unable to cause disease in humans. This viral vector has been tested for safety in other vaccines for Ebola, Middle East respiratory syndrome (MERS) and influenza. This vaccine utilises the full length SARS-CoV-2 spike protein DNA inserted into the viral vector.

On 16 February 2021, the University of Oxford/AstraZeneca COVID-19 vaccine (COVID-19 Vaccine AstraZeneca) was granted provisional registration in Australia by the Therapeutic Goods Administration for use in those ≥18-years of age for the prevention of COVID-19 disease caused by SARS-CoV-2.

Clinical trials

Pre-clinical (animal) trials were conducted in rhesus macaques, mice and ferrets. These trials showed that there were no adverse safety events, no evidence of immune enhanced inflammatory disease and a balanced immune response was induced. In animals, the vaccine appeared to reduce disease severity, but did not prevent infection or transmission (nasal shedding of the virus still occurred).

Phase 1/2 clinical trials were conducted in UK and recruited over one thousand participants in April and May 2020. Phase 2/3 clinical trials will be conducted in 50,000 participants globally (UK, USA, Brazil, South Africa and Kenya), with recruitment starting in July 2020. Interim results of Phase 3 studies, from over 10,000 participants, were published in the Lancet on 8 December 2020.

Safety profile

The Phase 1/2 results showed that the vaccine was safe but had higher reactogenicity than the control vaccine. Symptoms mainly occurred in the day following vaccination and self-resolved. Pain and tenderness at the injection site (83%), fatigue (68%) and headache (70%) were the most common symptoms in participants receiving the ChAdOx1 nCoV-19 vaccine. Fever occurred in 18% and flu-like symptoms of malaise (61%) and muscle ache (60%) were also common.

Phase 2/3 results showed similar reactions to those seen in Phase 1/2 trials but reactions were less common in older adults (aged over 55 years) and after the second dose. Most of the reported local and systemic adverse events were mild to moderate in severity.

Of the nearly 24,000 trial volunteers, only three of the 175 reported serious adverse events were possibly related to the vaccine and more than half of these events occurred in the control arm.

There have been two trial pauses due to initially unexplained illnesses; these were reviewed by independent experts before restarting the trials. One case of transverse myelitis was reported two weeks after ChAdOx1 nCoV-19 booster vaccination and was possibly related to vaccination. There were two additional cases of transverse myelitis that were determined to be unlikely to be related to vaccination by an independent committee of neurological experts. One case was due to pre-existing, but previously unrecognised, multiple sclerosis and the second case occurred in the control arm.

These Phase 3 trials were open to people with many underlying health conditions, however immunocompromised and pregnant people were excluded. Data is currently unavailable for children; they will be recruited in the later stages of Phase 3 trials, once extensive safety data is available from adult studies.

Immunogenicity

The ChAdOx1 nCoV-19 vaccine induced a specific antibody response to the SARS-CoV-2 spike protein after a single dose; this response was boosted after the second dose. Similar immune responses were seen across all age groups, including those aged 70 years and older. Regardless of age or vaccine dose, similar patterns were also observed with neutralising antibody responses and spike-specific T-cell responses.

Vaccine efficacy

Interim analysis of the Phase 3 trials was published on 8 December 2020. There were 11,636 participants (7,548 in the UK and 4,088 in Brazil) included in the interim primary efficacy analysis.

In participants who received two standard doses (5 × 1010 viral particles), vaccine efficacy was 62.1%. A subset in the UK trial received a half dose as their first dose and a standard dose as their second dose; in this cohort vaccine efficacy was 90.0%.

Overall vaccine efficacy across both groups was 70.4%. Further Phase 3 testing is underway to verify these results.

Vaccine efficacy in older age groups (over 55 years of age) could not be assessed in the interim analysis, but will be determined in future analyses once more data is accrued. This will be important data to review given the increasing morbidity and mortality seen with increasing age. Noting immunogenicity studies showed older adults do develop a robust immune response, similar to those seen in younger volunteers.

Resources

Authors: Daniela Say (MVEC Immunisation Fellow) and Nigel Crawford (Director SAEFVIC, Murdoch Children’s Research Institute)

Date: January 2021

Reviewed by: Rachael McGuire (MVEC Education Nurse Coordinator)

Updated: February 2021

Materials in this section are updated as new information and vaccines become available. The Melbourne Vaccine Education Centre (MVEC) staff regularly reviews materials for accuracy.

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