ccUEarly stage results from the Phase I/II clinical trial of the UK’s chimpanzee adenovirus viral vector (ChAdOx1) COVID-19 vaccine candidate reveal that the vaccine is safe and causes side effects. The vaccine also provoked a T cell response within 14 days of vaccination and an antibody response with 28 days.

According to researchers, an ideal vaccine to combat SARS-CoV-2 (the coronavirus causing the COVID-19 pandemic) should be effective after one or two vaccinations, work in target populations including older adults and those with other health conditions, confer protection for a minimum of six months and reduce onward transmission of the virus to contacts. While the current trial is too preliminary to establish if the vaccine meets these criteria, other Phase II and III trials are ongoing to establish if it protects against SARS-CoV-2 infection. Phase III trials are taking place in the UK, Brazil and South Africa.

Explaining how the vaccine works, study lead author Professor Andrew Pollard, University of Oxford, UK, said: “The new vaccine is a chimpanzee adenovirus viral vector (ChAdOx1) vaccine that expresses the SARS-CoV-2 spike protein. It uses an adenovirus that infects chimpanzees, which has been weakened so that it cannot cause any disease in humans and is genetically modified to code for the spike protein of the human SARS-CoV-2 virus. This means that when the adenovirus enters vaccinated people’s cells it also delivers the spike protein genetic code. This causes these cells to produce the spike protein and helps teach the immune system to recognise the SARS-CoV-2 virus.”

The trial included 1,077 healthy adults aged 18-55 years with no history of COVID-19 and took place in five UK hospitals between 23 April and 21 May 2020. The data included in the paper covered only the first 56 days of the trial.

The participants either received the new COVID-19 vaccine (543 participants) or the meningococcal conjugate vaccine (534 people). 113 participants (56 given the COVID vaccine, and 57 in the control group) were also asked to take paracetamol before and for 24 hours after their vaccination to help reduce vaccine-associated reactions.

All participants gave blood samples and underwent clinical assessments to determine if the vaccine was safe and whether it provoked an immune response. Participants were also asked to record any adverse events throughout the trial.

The participants were split into four groups: Group 1 (88 people) had additional safety monitoring to form the Phase I part of the trial and had their antibody and T cell responses assessed; Group 2 (412 people) had extra blood taken to assess for antibody and T cell responses; and group 4 (567 people) had serum taken to assess for antibody response only. In groups 1, 2 and 4 half the participants received the COVID-19 vaccine and half received the control vaccine. Group 3 (10 people) received only the COVID-19 vaccine and were given an extra dose of vaccine 28 days after the first dose to determine safety and whether this boosted antibody and T cell responses.

There were no serious adverse events associated with the vaccine. Fatigue and headache were the most commonly reported reactions of participants given the COVID-19 vaccine. Other common side effects included pain at the injection site, muscle ache, malaise, chills, feeling feverish and high temperature.

Participants taking paracetamol around their vaccination had reduced pain, chills, feeling feverish, muscle ache, headache and malaise in the two days following vaccination. In addition, in the 10 people who received the extra dose of the COVID-19 vaccine, side effects were less common after the second dose.

The investigators reported that the vaccine induced strong T cell responses targeting the spike protein, peaking 14 days after vaccination with this level declining slightly by day 56 of the trial. The T cell response did not increase with a second dose of the vaccine, which is consistent with other vaccines of this kind.

Antibody responses peaked by day 28 and remained high until the measurement at day 56 in the trial for those given a single vaccine. This response was boosted by a second dose.

The team also revealed that 28 days after vaccination, neutralising antibody responses against SARS-CoV-2 were detected in 32 of 35 participants and in 35 of 35 participants who received a single dose of the COVID-19 vaccine. These responses were present in all participants who had a booster dose of the vaccine.

The authors found that taking paracetamol did not affect immunogenicity of the COVID-19 vaccine.

Co-author, Professor Sarah Gilbert, University of Oxford, UK, said: “There is still much work to be done before we can confirm if our vaccine will help manage the COVID-19 pandemic, but these early results hold promise. As well as continuing to test our vaccine in Phase III trials, we need to learn more about the virus – for example, we still do not know how strong an immune response we need to provoke to effectively protect against SARS-CoV-2 infection. If our vaccine is effective, it is a promising option as these types of vaccine can be manufactured at large scale. A successful vaccine against SARS-CoV-2 could be used to prevent infection, disease and death in the whole population, with high risk populations such as hospital workers and older adults prioritised to receive vaccination.”

The authors note some limitations: more research will be needed to confirm their findings in other patient populations, including older age groups and those with other health conditions; and that a small number of participants had detectable neutralising antibodies and T cell responses against SARS-CoV-2 spike protein before vaccination, likely to be due to past asymptomatic infection.

The authors say the participants recruited in this study will be followed-up for at least one year to continue to study the vaccine’s safety and the immune response it provokes.

The results are published in The Lancet.