The Oxford/AstraZeneca COVID-19 Vaccine: Encouraging Interim Results

The ChAdOx1 nCoV-19 vaccine (also known as AZD1222), developed by Oxford University and AstraZeneca, is a chimpanzee adenovirus-vectored vaccine that targets the SARS-CoV-2 spike glycoprotein. Two reports detail the vaccine's safety and immunogenicity in various populations (including older adults) and provide an interim efficacy analysis of four pooled studies.

In a blinded phase 2 study, researchers examined the safety and immunogenicity of a low dose (LD; 2.2x10¹⁰ virus particles) or standard dose (SD; 3.5–6.5x10¹⁰ virus particles) of vaccine administered as either one or two doses (prime + boost 28 days later), with the meningococcal MenACWY vaccine as a control. A total of 560 participants were enrolled (160 aged 18–55, 160 aged 56–69, and 240 aged ≥70; 50% female, 95% white, and 98% nonsmokers).

Local and systemic reactions were more common in those receiving ChAdOx1 nCoV-19 than those receiving control. Injection site pain and tenderness (the most common local adverse reactions) were reported after two SDs in 88% of participants aged 18–55, 73% of those aged 55–69, and 61% of those 70 or older. Fatigue, headache, fever, and myalgias (the most common systemic adverse reactions) were reported by 86%, 77%, and 65% of participants in the three age cohorts. Anti-spike IgG responses at day 28 were similar after prime vaccination with SD or LD, but decreased with advancing age. After boost vaccination, median anti-spike IgG responses were similar across the three age cohorts regardless of dose. By 14 days after the boost, >99% of participants had neutralizing antibody responses. T-cell responses peaked at day 14 after prime vaccination, were similar in all groups regardless of age and dose, and did not increase significantly after boost vaccination.

In an interim efficacy analysis pooling the results of four randomized, controlled trials in the U.K., Brazil, and South Africa that included 11,636 participants who had been assigned to either two SDs or an LD followed by an SD of vaccine, 131 cases of symptomatic COVID-19 occurred >14 days after the second dose (30 of 5807 participants in the vaccine arm and 101 of 5829 participants in the control arm) yielding an efficacy of 70.4% (95% confidence interval, 54.8–80.6). In participants who received two SDs, vaccine efficacy was 62.1%. In the subset receiving an LD followed by an SD, efficacy was 90.0%. Ten participants, all in the control arm, were hospitalized with COVID-19, two of whom had severe disease (including one who died). With 74,341 months of safety follow-up, three adverse events were classified as possibly related to vaccine of which only one was in the COVID-19 vaccine group.