Data from the first 56 days of the ongoing trial, published today in The Lancet, suggest the vaccine is 'safe', causes few side-effects, and induces strong cellular and humoral immunity – provoking a T-cell response within 14 days of vaccination, and an antibody response with 28 days.
The new vaccine uses a weakened version of a chimpanzee adenovirus (common cold virus), which has been genetically modified to code for the spike protein of the human SARS-CoV-2 virus. When the adenovirus enters a cell it delivers the spike protein genetic code, which instructs the cell to produce the spike protein, and helps teach the immune system to recognise the SARS-CoV-2 virus.
Study co-author Professor Sarah Gilbert, from the University of Oxford, commented: '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.'
Between 23 April and 21 May 2020, the randomised, controlled, single-blind trial enrolled 1077 healthy adults aged 18–55 years with no history of COVID-19.
Participants received either the experimental COVID-19 vaccine or a licensed meningococcal conjugate vaccine (MenACWY); 113 participants were also asked to take paracetamol before and for 24 hours after their vaccination to lessen adverse reactions.
Ten participants assigned to a non-randomised, unblinded prime-boost group received a two-dose schedule of the COVID-19 vaccine, with the booster vaccine administered 28 days after the first dose.
The COVID-19 vaccine was found to have an acceptable safety profile and there were no serious adverse events.
Local and systemic reactions were more common in the COVID-19 group, although many were reduced by use of prophylactic paracetamol, including pain, feeling feverish, chills, muscle ache, headache, and malaise.
Fatigue and headache were the most commonly reported reactions: fatigue was reported by 70% of participants given the COVID-19 vaccine without paracetamol (71% of those with paracetamol), versus 48% of those given the MenACWY vaccine without paracetamol; headache was reported by 68% of the COVID-19 group without paracetamol (61% with paracetamol), versus 41% of participants in the MenACWY group without paracetamol.
T-cell response to the SARS-CoV-2 spike protein peaked at day 14 and declined slightly by day 56; the antibody response peaked by day 28 and remained high at day 56. Antibody levels were boosted in people who received a second dose.
Neutralising antibody responses against SARS-CoV-2 were detected in more than 90% of participants (32/35) at 28 days after a single dose, and in 100% of the participants who received a booster dose.
Taking paracetamol did not affect the immunogenicity of the COVID-19 vaccine.
The authors note 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 as individuals with recent COVID-19-like symptoms or a history of positive PCR test for SARS-CoV-2 were excluded from the study.
The trial participants will continue to be monitored for at least a year to further characterise the vaccine’s safety and immunogenicity.
Phase II and III trials are now underway in UK, Brazil and South Africa to establish whether the vaccine protects against COVID-19 infection. These trials also aim to confirm the current findings in different groups of people – including older age groups, those with other health conditions, and in ethnically and geographically diverse populations.
Professor Gilbert added: '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.'
In a linked editorial discussing the results of the UK study and similarly promising early results of a Chinese phase II trial of another COVID-19 adenovirus-vector vaccine, Naor Bar-Zeev and William J Moss from the International Vaccine Access Center at Johns Hopkins Bloomberg School of Public Health in the US, caution that the first adenovirus-vector vaccine, against Ebola, was only approved in Europe earlier this month. They say: 'Much remains unknown about these and other COVID-19 vaccines in development, including longevity of response and immunogenicity in older adults or other specific groups, such as those with comorbidities who are often excluded from clinical trials, or ethnic or racial groups more severely affected by COVID-19.'