Interim results from the ongoing Phase II/III COV002 trial of AZD1222 in the UK, led by the University of Oxford demonstrated lower local and systemic reactions in older adults (≥56-69 years and ≥70 years) than younger adults (≥18-55 years) and generated similar robust immune responses against the SARS-CoV-2 virus across all adult age groups.
COV002 is a blinded, multi-centre, randomised, controlled Phase II/III trial in 12,390 participants in the UK. In the Phase II trial, participants aged 18 years or over are randomised to receive either one or two standard or low doses, given one month apart of AZD1222, or the MenACWY comparator vaccine, by intramuscular injection.
The results published in The Lancet confirm that transient, predominantly mild, local and systemic reactions were common in the AZD1222 group and were comparable to interim data previously reported with the vaccine from the Phase I/II trial and other adenoviral vector vaccines.1-4 They included temporary injection site pain and tenderness and fatigue, headache, feverishness and myalgia. Fewer reactions were experienced after a second dose of AZD1222 and with the lower dose. The frequency of reactions were also reduced with increasing age.
Antibody responses to the SARS-CoV-2 virus spike protein were detected by day 28 in 100% participants, regardless of age or vaccine dosage and continued to rise after a second dose of AZD1222. Neutralising activity was seen in 100% participants by day 14 after receiving a second standard dose, regardless of age. T-cell responses were induced, peaking by day 14 after the first dose and were maintained two months after injection, regardless of age and dosage.
Mene Pangalos, Executive Vice President, BioPharmaceuticals R&D, said: “It is essential that a COVID-19 vaccine can be effective across a broad age range, particularly in older individuals where they are disproportionately at risk of severe COVID-19 disease. The Phase II interim data for AZD1222 suggests older individuals have lower reactogenicity whilst still maintaining a robust immune response.”
Clinical trials of AZD1222 are ongoing globally across UK, US, Brazil, South Africa, Japan, Russia and Kenya recruiting up to 60,000 participants across a broad age range and diverse racial, ethnic and geographic groups. Initial late-stage trial results are expected before the end of the year depending on the infection rate within the trial communities.
AstraZeneca continues to fulfil its commitment to support broad and equitable access to the vaccine at no profit during the pandemic, should clinical trials prove successful and approved by regulators. Global supply capacity, including our out-licensing partners, has been secured towards three billion doses, built over twelve regional supply chains and involving more than twenty contracting manufacturing organisations, including AstraZeneca manufacturing sites. Rapid progress is being made across every aspect of vaccine manufacturing from drug substance, formulation, filling and packaging. It is important to align delivery of the final drug product with regulatory approval to ensure maximum remaining shelf-life.
Immune correlates of protection to COVID-19 disease5
Correlates of protection for a vaccine against COVID-19 have not yet been defined. High levels of neutralising antibodies have been demonstrated in individuals who have recovered from SARS-CoV-2 infection. In addition, emerging data suggest that a T-cell response could play an important role in mitigation of the disease. Some individuals who have been infected with the virus but remained asymptomatic, have developed a robust T-cell response with an absence of detectable antibodies. Rapid induction of antibodies and T-cells against the SARS-CoV-2 virus may be important in protection against COVID-19.
COV002 is a blinded, multi-centre, randomised, controlled Phase II/III trial assessing the safety, efficacy, and immunogenicity of AZD1222 compared to placebo for the prevention of COVID-19, in 12,390 participants in the UK. Trial participants to date are aged 18 years or over, who are healthy or have medically stable chronic diseases, and are at increased risk for being exposed to the SARS-CoV-2 virus are randomised to receive one or two intramuscular doses of AZD1222 or MenACWY comparator vaccine. Randomisation is stratified by age, ≥18 to 55 years, 56-69 years, and ≥70 years, in a 1:1, 3:1 or 5:1 ratio, respectively. In the Phase II trial participants received either one or two doses of a standard dose (3.5-6.55 x1010 viral particles) or low dose (2.2 x1010 viral particles).
1. Folegatti, P.M., et al., Safety and immunogenicity of the ChAdOx1 nCoV-19 vaccine against SARS-CoV-2: a preliminary report of a phase 1/2, single-blind, randomised controlled trial. The Lancet 2020; 396 (10249): 467-78.
2. Tapia, M.D., et al., Safety, reactogenicity, and immunogenicity of a chimpanzee adenovirus vectored Ebola vaccine in children in Africa: a randomised, observer-blind, placebo-controlled, phase 2 trial. Lancet Infect Dis 2020; 20(6): 719-30.
3. Coughlan, L., et al., Heterologous Two-Dose Vaccination with Simian Adenovirus and Poxvirus Vectors Elicits Long-Lasting Cellular Immunity to Influenza Virus A in Healthy Adults. EBioMedicine 2018; 29: 146-54.
4. Wilkie, M., et al., A phase I trial evaluating the safety and immunogenicity of a candidate tuberculosis vaccination regimen, ChAdOx1 85A prime - MVA85A boost in healthy UK adults. Vaccine, 2020. 38(4): 779-89.
5. Sekine, T., et al., Robust T cell immunity in convalescent individuals with asymptomatic or mild COVID-19. BioRxiv, 2020. preprint doi: https://doi.org/10.1101/2020.06.29.174888.