Randomized Controlled Trial
Study population and setting
This paper is focused on safety and efficacy results from the phase 2 portion of a phase 2/3 trial testing Oxford and AstraZeneca’s ChAdOx1 vaccine against SARS-CoV-2. The trial took place at 20 sites across the UK, with results from two sites highlighted here. The study took place between May 30 and August 8, 2020 and included 560 participants. Patients were divided into three age groups: 18-55, 56-69, and 70 years and older, with 400 of the participants considered older adults (ages 56+ years). The vaccine was given in a single or two dose regimen, 28 days apart. Participants were given either a low (2.2 x 1010 viral particles) or standard dose (3.5 – 6.5 x 1010 viral particles) of ChAdOx1 nCoV-19, or a placebo vaccine. Clinical and immunologic data was collected on days 0, 7, 14, and 28 after both prime and booster doses, if applicable.
Summary of Main Findings
This trial observed no serious adverse events related to the safety of the vaccine. Fatigue, headache and muscle pain were the most commonly reported systemic adverse events, as well as pain at injection site. However, reactogenicity to the inoculation decreased with increasing age. Immunogenicity was assessed by measuring levels of neutralizing antibodies and immune response after vaccination. There was an increase in receptor binding domain (a part of the viral spike protein) specific neutralizing antibodies one month after the booster dose, while there was no increase in antibodies specific to the adenoviral vaccine vector itself. Neutralizing antibody titers were observed at comparable levels across all age and dose groups by one-month post-booster vaccine. IFN-γ levels peaked following the prime dose, but did not increase significantly after the booster dose.
This vaccine uses a simian adenovirus instead of one that normally infects humans in order to combat the issue of pre-existing immunity to the adenoviral vector. Two different doses, as well as two different dosing strategies, were studied here. Additionally, a wide age range of older adults were enrolled as participants. This is key because they are a critical population to be vaccinated since they are much more susceptible to severe cases of COVID-19.
The participants enrolled in this trial were mainly white, and with few co-morbidities. Future studies will need to address more diverse populations. The low dose of the vaccine was produced by two separate manufacturers, and as a consequence two different injection volumes were used, which could have influenced local reactogenicity. Neutralizing antibodies are still being used as a correlate of protection here, but no true correlate of protection has yet been defined. Finally, the oldest participants averaged in the low 70s age range, and this may not be representative of those living in long-term care facilities and other older individuals who will need the vaccine.
Safety and immunogenicity results of Oxford and AstraZeneca’s phase 2 adenoviral vectored vaccine trial including a population of older adults.
This review was posted on: 14 December 2020