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Single dose administration, and the influence of the timing of the booster dose on immunogenicity and efficacy of ChAdOx1 nCoV-19 (AZD1222) vaccine

Our take —

This study, available as a preprint and thus not yet peer reviewed, presents further data on the efficacy of the ChAdOx1 nCoV-19 (Oxford/AstraZeneca) vaccine. The authors demonstrated that a single dose is efficacious against symptomatic COVID-19 for at least 90 days. Higher vaccine efficacy was observed when the time between the first and second doses was longer (12+ weeks vs. <6 weeks). Additionally, asymptomatic cases decreased with vaccination suggesting a potential impact on transmission.

Study design

Randomized Controlled Trial

Study population and setting

Data is presented from phase III (conducted in the United Kingdom and Brazil) and phase I/II trials (conducted in the United Kingdom and South Africa) including 17,177 participants of the ChAdOx1 nCoV-19 (Oxford/AstraZeneca) vaccine. Previous findings and protocol descriptions can be found here. Importantly, participants were swabbed weekly, regardless of symptoms, to assess incidence of asymptomatic infection. ChAdOx1 nCoV-19 vaccine is a chimpanzee adenoviral vectored vaccine encoding the full-length SARS-CoV-2 S protein. Vaccine was administered in either a Standard Dose-Standard Dose (SDSD) regimen or Low Dose-Standard Dose (LDSD) regimen. The vaccine has been authorized for emergency use for adults over 18 years old in the UK and other countries using a 2-dose regimen administered 4-12 weeks apart. This report presents data from an additional month of follow-up from ongoing trials as well as analysis of a self-selected single dose cohort, and a cohort who received their second dose at an increased time interval.

Summary of Main Findings

Overall efficacy of the ChAdOx1 nCoV-19 vaccine was 66.7%. For the LDSD regimen, vaccine efficacy was 80.7%. For the SDSD regimen, overall vaccine efficacy was 63.1%. However, when vaccine doses were spaced more than 12 weeks apart, efficacy rose to 82.4%. Anti-spike antibodies and neutralizing antibody titers were also higher at 6 months post-vaccination in groups with longer time between doses. This suggests that the difference in efficacy between the SDSD and LDSD groups that was previously noted may be due to the timing of vaccination, rather than dosage, as the LDSD group had much more incidence of delayed second doses. In these studies, 130 cases of asymptomatic cases were observed 14 days after the booster. There was 47.2% efficacy against asymptomatic cases in the LDSD and SDSD combined data. A single dose did not show protection against asymptomatic infection. However, this was only tracked to 60 days post vaccination, and only 11 total cases were observed in this group.

Study Strengths

This study included weekly swabs of participants to assess asymptomatic infection. This is very important to understanding the full efficacy of this vaccine.

Limitations

This analysis was all performed post-hoc, and therefore has room for bias. These studies were not originally designed to assess differences in dosing intervals or to assess a single dose. Additionally, the 95% confidence intervals for much of the estimates were very large, making distinctions between some of the groups difficult to interpret. While efficacy observed against asymptomatic cases suggests that transmission might be reduced with this vaccine, this has not been directly demonstrated. The duration of protection from a single dose vaccine is not clear. Further follow-up of all groups is needed.

Value added

These studies showed that a single dose of the ChAdOx1 nCoV-19 (Oxford/AstraZeneca) vaccine was efficacious for at least 90 days. A booster shot did significantly increase the efficacy of the vaccine. These studies also indicated that previous differences in efficacy noted with different dosing amount of ChAdOx1 nCoV-19 vaccine were likely due to the amount of time between doses, not difference in dose amounts. This supports continued use of the SDSD regimen.

This review was posted on: 11 February 2021