Vaccines to prevent COVID-19 infection are crucial for an effective global pandemic response. In The Lancet, Merryn Voysey and colleagues report the updated primary efficacy results for the Oxford–AstraZeneca ChAdOx1 nCoV-19 (AZD1222) vaccine from three single-blind, randomised controlled trials in the UK and Brazil and one double-blind study in South Africa.

A subsequent report of the same group, based on an interim analysis of four randomised controlled trials done in Brazil, South Africa, and the UK,
suggested an overall vaccine efficacy of 70·4% (95·8% CI 54·8–80·6), with a higher efficacy of 90% (95% CI 67·4–97·0) in those who received a low dose (2·2×10¹⁰ viral particles per dose) followed by a standard dose (5×10¹⁰ viral particles per dose), and a vaccine efficacy of 62·1% (95% CI 41·0–75·7) in those who received two standard doses (4 weeks apart).

The UK Government decided on a policy of administering as many first
doses as possible and delaying the second dose of the ChAdOx1 nCoV-19 vaccine until 12 weeks after the first dose. Although this policy was criticised, the latest results reported by Voysey and colleagues on The Lancet provide a necessary evidence-based justification for the decision.

The study is based on an updated analysis of 17178 participants (9696 [56·4%] were women, 12975 [75·5%] were white, and 14413 [83·9%] were aged 18–55 years, 1792 [10·4%] aged 56–69 years, and 973 [5·7%] aged
70 years or older) from the four trials.The pooled results from these trials (including participants who received two standard doses and those who received a low dose followed by a standard dose) showed an overall vaccine
efficacy against symptomatic COVID-19 more than 14 days after the second dose of 66·7% (95% CI 57·4–74·0).

Vaccine efficacy was 63·1% (51·8–71·7) in those who received two standard doses and 80·7% (62·1–90·2) in those who received the low dose plus standard dose. Notably, in exploratory analyses, vaccine efficacy after
a single standard dose was 76·0% (59·3–85·9) from day 22 to day 90, and antibody levels were maintained during this period with minimal waning.

Supporting a longer-interval immunisation strategy, vaccine efficacy
was significantly higher at 81·3% (60·3–91·2) after two standard doses given at an interval of 12 weeks or longer, compared with 55·1% (33·0–69·9) when given less than 6 weeks apart.

These findings were supported by immunogenicity studies done in participants who were younger than 55 years, showing anti-SARS-CoV-2 spike IgG antibody responses more than two-fold higher in those who had a dose interval of at least 12 weeks than in those who had an interval of less than 6 weeks (geometric mean ratio 2·32 [95% CI 2·01–2·68]).

Modelling analyses showed an increase in vaccine efficacy after two standard doses from 55·1% (95% CI 33·0 to 69·9) with an interval of less than
6 weeks to 81·3% (60·3 to 91·2) with an interval of at least 12 weeks.

A single standard dose had an efficacy against symptomatic COVID-19 in the first 90 days of 76·0% (59·3 to 85·9), yet provided no protection
against asymptomatic infection (vaccine efficacy
–17·2% [–248·6 to 60·6]).

Notably, efficacy against any nucleic acid amplification test-positive cases, including symptomatic and asymptomatic or unknown cases, was 63·9% (46·0 to 75·9) after a single standard dose, suggesting the possibility of reducing viral transmission.

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