The Lancet: Phase 2 trial of Oxford COVID-19 vaccine in healthy older adults finds it is safe and provokes immune response

November 19, 2020

Peer-reviewed / Randomised Controlled Trial / People

**There will be a UK Science Media Centre briefing at 10.15am UK time on Thursday 19th November about this study. Please see details in notes to editors** The UK's vaccine against SARS-CoV-2 shows similar safety and immunogenicity results in healthy older adults (aged 56 years and over) to those seen in adults aged 18-55 years. The promising early stage results are published in The Lancet.

The phase 2 trial finds that the vaccine causes few side effects, and induces immune responses in both parts of the immune system in all age groups and at low and standard dose - provoking a T cell response within 14 days of the first dose of vaccination (ie, a cellular immune response, it could find and attack cells infected with the virus), and an antibody response within 28 days of the booster dose of vaccination (ie, humoral immune response, it could find and attack the virus when it was circulating in the blood or lymphatic system). Phase 3 trials are ongoing to confirm these results - as well as how effective the vaccine is in protecting against infection with SARS-CoV-2 - in a broader range of people, including older adults with underlying health conditions.

Study lead author Professor Andrew Pollard, University of Oxford, UK, says: "Immune responses from vaccines are often lessened in older adults because the immune system gradually deteriorates with age, which also leaves older adults more susceptible to infections. As a result, it is crucial that COVID-19 vaccines are tested in this group who are also a priority group for immunisation." [1]

Co-author Dr Maheshi Ramasamy, University of Oxford, UK, adds: "The robust antibody and T-cell responses seen in older people in our study are encouraging. The populations at greatest risk of serious COVID-19 disease include people with existing health conditions and older adults. We hope that this means our vaccine will help to protect some of the most vulnerable people in society, but further research will be needed before we can be sure." [1]

The new study is the fifth published clinical trial of a vaccine against SARS-CoV-2 tested in an older adult population. Other COVID-19 vaccines have also been shown to generate immune responses in older adults, but it can be difficult to compare results between different studies. One study has shown similar immune responses in young and old adults (Moderna mRNA vaccine), while other trials have suggested lower measured responses in older adults, compared to younger adults receiving the same vaccine (CanSino single dose adenovirus-vector vaccine, Pfizer/BioNTech mRNA vaccine, and SinoPharm/Beijing Institute of Biological Products inactivated viral vaccine).

In the phase 2 trial published today, 560 participants (160 aged 18-55 years, 160 aged 56-69 years, and 240 aged 70 or over) were split into 10 groups [2] where they received either the ChAdOx1 nCoV-19 vaccine at a low or standard dose, or a control vaccine (the meningococcal conjugate vaccine). Participants aged over 55 years were also split into groups and either given a single dose of vaccine, or two doses 28 days apart.

Study recruitment occurred during a national lockdown in the UK when vulnerable individuals were advised to self-isolate. For this reason, the study includes only healthy participants and not those with co-morbidities or who are frail. Before receiving the vaccine, all participants had a blood test to determine if they had previously been infected with SARS-CoV-2. Those who had antibodies for SARS-CoV-2 were excluded, except for 18-55-year-olds in the standard dose double vaccine groups.

Following vaccination, participants were observed for a minimum of 15 minutes in case of any immediate adverse events, and participants recorded any adverse events for seven days afterwards. Participants will continue to be monitored for any serious adverse events for one year following final vaccination (the year long data are not yet available).

Participants aged 18-55 years who received two standard doses of the Oxford COVID-19 vaccine and all participants aged 56 years or over had their immune responses assessed on the day of vaccination, then 1, 2 and 4 weeks after their first and second vaccination.

Adverse reactions to the ChAdOx1 nCoV-19 vaccine were mild (the most common effects were injection-site pain and tenderness, fatigue, headache, feverishness and muscle pain), but more common than seen with the control vaccine. Thirteen serious adverse events occurred in the six months since the first dose was given, none of which were related to either study vaccine.

Adverse effects were less common in older adults than in younger adults (within seven days of one standard dose of ChAdOx1 nCoV-19, local symptoms such as temporary pain, tenderness, redness, and swelling at the site of the injection occurred in 88%, 43/49 18-55 year olds, 73%, 22/30 56-69 year olds, and 61%, 30/49 people aged 70 or over. Within 7 days of injection, systemic symptoms such as temporary fatigue, headache, malaise, feverishness, and muscle aches occurred in 86%, 42/49 18-55 year olds, 77%, 23/30 56-69 year olds, and 65%, 32/49 people aged 70 or over), and similar levels of local symptoms were seen after the first and booster doses of the Oxford COVID-19 vaccine in older adults, while there were few systemic symptoms following the booster dose.

The COVID-19 vaccine had similar immunogenicity across all age groups after a boost dose.

The ChAdOx1 nCoV-19 vaccine induced antibodies against the SARS-CoV-2 spike protein and receptor binding domain 28 days after a single low or standard dose across all age groups. Following the booster dose of the vaccine, antibody levels increased at day 56 of the trial, irrespective of dose or participant age. The same was seen with levels of neutralising antibodies at day 42, two weeks after the booster vaccine dose. By 14 days after the boost dose, 208 of 209 (more than 99%) participants (selected from participants of all ages and doses) had neutralising antibody responses.

T cell responses against the SARS-CoV-2 spike protein peaked 14 days after first vaccination, regardless of age and low or standard vaccine dose.

Co-author, Professor Sarah Gilbert, University of Oxford, UK, says: "The WHO has outlined a number of critical factors for COVID-19 vaccines, including that they must be targeted at the most at-risk groups including older adults. They must also be safe, effective in preventing disease and/or transmission, and provide at least six months of protection for people frequently exposed to the virus - such as healthcare workers. Our new study answers some of these questions about protecting older adults, but questions remain about effectiveness and length of protection, and we need to confirm our results in older adults with underlying conditions to ensure that our vaccine protects those most at risk of severe COVID-19 disease." [1]

The authors note some limitations to their study, including that the participants in the oldest age group had an average age of 73-74 years and few underlying health conditions, so may not be representative of the general older population, including those living in residential care settings or over 80 years of age. Larger studies are now underway to evaluate immunogenicity, safety and efficacy in older adults with a wider range of comorbidities. Lastly, the authors note that almost all participants of all ages were white and non-smokers, and may not be representative of the general population, but people from a range of backgrounds, countries and ethnicities are being included in the phase 3 trial of this vaccine.

Writing in a linked Comment, lead author Dr Melissa Andrew, Dalhousie University, Canada, who was not involved in the study, says: "It is encouraging that more studies in older adult populations are underway and will hopefully bring opportunities to implement nuanced analyses of how underlying health status and frailty affect vaccine safety, reactogenicity, immunogenicity, and efficacy in older adults in real-world settings. Older adults (across the full spectrum of frailty) and those who care about them are eagerly awaiting this progress towards safe and effective COVID-19 vaccines."

This study was funded by UK Research and Innovation, National Institutes for Health Research (NIHR), Coalition for Epidemic Preparedness Innovations, NIHR Oxford Biomedical Research Centre, Thames Valley and South Midlands NIHR Clinical Research Network, and AstraZeneca. A full list of the authors and their institutions is available in the paper.

The labels have been added to this press release as part of a project run by the Academy of Medical Sciences seeking to improve the communication of evidence. For more information, please see: if you have any questions or feedback, please contact The Lancet press office

[1] Quote direct from author and cannot be found in the text of the Article.

[2] See figure 1 for full detail. 300 participants were enrolled to the low-dose cohort, and 260 to the standard-dose cohort.

In the low-dose cohort, there were 100 18-55 year olds (50 in the two-dose COVID-19 vaccine group, and 50 in the two-dose control group), 80 56-69 year olds (30 in the one-dose COVID-19 vaccine group, 10 in the one-dose control group, 30 in the two-dose COVID-19 vaccine group, and 10 in the two-dose control group), and 120 people aged over 70 (50 in the one-dose COVID-19 vaccine group, 10 in the one-dose control group, 50 in the two-dose COVID-19 vaccine group, and 10 in the two-dose control group).

In the standard-dose cohort, there were 60 18-55 year olds (50 in the two-dose COVID-19 vaccine group, and 10 in the two-dose control group), 80 56-69 year olds (30 in the one-dose COVID-19 vaccine group, 10 in the one-dose control group, 30 in the two-dose COVID-19 vaccine group, and 10 in the two-dose control group), and 120 people aged over 70 (50 in the one-dose COVID-19 vaccine group, 10 in the one-dose control group, 50 in the two-dose COVID-19 vaccine group, and 10 in the two-dose control group).

For interviews with the Article author, please contact the University of Oxford press office: E) T) +44 (0) 1865 280528

Please be aware, due to limited availability, the authors are not available for comment prior to the embargo lifting. They will be available for further questions at a UK Science Media Centre briefing at 10.15am UK time on Thursday 19th November. To register to attend, please contact Fiona Lethbridge:

The Lancet

Related Vaccination Articles from Brightsurf:

US adults' likelihood of accepting COVID-19 vaccination
In this survey study of U.S. adults, vaccine-related attributes and political characteristics were associated with self-reported preferences for choosing a hypothetical COVID-19 vaccine and self- reported willingness to receive vaccination.

Vaccination insights
While scientists race to develop and test a vaccine effective against SARS-CoV-2, the virus that causes COVID-19, recent studies have indicated that countries with widespread BCG vaccination appear to be weathering the pandemic better than their counterparts.

Wording of vaccination messages influences behavior
An experiment by Washington State University researchers revealed that relatively small differences in messages influenced people's attitudes about the human papillomavirus or HPV vaccine, which has been shown to help prevent cancer.

Addressing HPV vaccination concerns
Research from the Harvard Pilgrim Health Care Institute finds a promising avenue for addressing vaccine hesitancy around HPV vaccine.

Virtual reality could help flu vaccination rates
Using a virtual reality simulation to show how flu spreads and its impact on others could be a way to encourage more people to get a flu vaccination, according to a study by researchers at the University of Georgia and the Oak Ridge Associated Universities in Oak Ridge, Tennessee.

Religion associated with HPV vaccination rate for college women
A survey of female college students finds 25% had not been vaccinated for HPV and religion may be a contributing factor.

Measles vaccination: 'All for one and one for all'
A commentary by researchers addresses the specter of clinical, ethical, public health and legal concerns that have been raised because of the recent measles outbreaks in New York.

New single vaccination approach to killer diseases
Scientists from the University of Adelaide's Research Centre for Infectious Diseases have developed a single vaccination approach to simultaneously combat influenza and pneumococcal infections, the world's most deadly respiratory diseases.

Vaccination may help protect bats from deadly disease
A new study shows that vaccination may reduce the impact of white-nose syndrome in bats, marking a milestone in the international fight against one of the most destructive wildlife diseases in modern times.

Parents reassured febrile seizures following vaccination not dangerous
New University of Sydney research finds that febrile seizures after vaccination are rare, not serious and are no different to febrile seizures due to other causes such as from a virus.

Read More: Vaccination News and Vaccination Current Events is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to