Vaccines to prevent COVID-19 infection are crucial for an effective global pandemic response. In The Lancet, Merryn Voysey and colleagues report updated primary efficacy results for the Oxford-AstraZeneca ChAdOx1 nCoV-19 vaccine (AZD1222) from three single-blind randomized controlled trials in the United Kingdom and Brazil and one double-blind study in South Africa.
The ChAdOx1 nCoV-19 vaccine received emergency use authorization in adults from the UK Medicines and Healthcare products Regulatory Agency in December 2020. A subsequent report, based on an interim analysis of four randomized controlled trials conducted in Brazil , South Africa and the United Kingdom, suggested an overall vaccine efficacy of 70.4% (95.8% CI 54.8-80.6), with a higher efficacy of 90% (95% CI 67.4-80.6). 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).
As a result of this interim data, and to achieve the greatest health benefit quickly, 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 later. from the first. dose.
Although this policy was criticized, the latest results reported by Voysey and colleagues provide a needed evidence-based justification for the decision.
The study is based on an updated analysis of 17,178 participants (9,696 [56.4%] were women, 12,975 [75.5%] were white, and 14,413 [83.9%] were between 18 and 55 years old, 1,792 [10 4 %] aged 56 to 69 years and 973 [5 7%] aged 70 years or older) from the four trials.
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 overall vaccine effectiveness against symptomatic COVID-19 more than 14 days after the second dose of the vaccine. 66% 7% (95% CI 57·4–74·0). Vaccine efficacy was 63·1% (51·8–71·7) in those given two standard doses and 80·7% (62·1–90·2) in those given the low dose plus the 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 decline. Supporting a longer interval immunization 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 more , compared with 55 · 1% (33 · 0-69 · 9) when administered less than 6 weeks apart.
These findings were supported by immunogenicity studies conducted in participants younger than 55 years, which showed more than twice as high anti-SARS-CoV-2 spike IgG antibody responses in those who had a dosing 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).
Modeling analyzes 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), but did not provide protection against asymptomatic infection (vaccine efficacy −17·2 % [−248 · 6 to 60 · 6]).
Notably, efficacy against any nucleic acid amplification test-positive case, 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.
Important limitations of the studies include the fact that these studies were not prospectively designed to establish whether vaccine efficacy differed by dose interval; therefore, these post-hoc exploratory findings could be biased. Other limitations are that participants were not randomized to dosing interval, only one of the four trials was double-blind, and single-dose recipients were self-selected.
Additionally, baseline characteristics between the single-dose and two-dose cohorts were substantially different, with an older median age, a higher proportion of male and non-white participants, and a lower proportion of health or social care workers. in the two-dose cohort. than in the single-dose cohort. Additionally, it is worth considering whether these results would hold with widespread circulation of more transmissible and lethal viral variants.
| The value of this study lies in providing evidence that a single dose of the ChAdOx1 nCoV-19 vaccine is highly effective within 90 days of vaccination, that a longer prime-boost interval results in greater efficacy of the vaccine. vaccine and that protection against COVID-19 symptoms is maintained despite a longer dosing interval. |
It provides much-needed evidence for the UK’s policy of extending the dosing interval to 12 weeks and for rapid mass immunization campaigns around the world. More studies are needed to evaluate whether a longer interval strategy would also offer greater vaccine efficacy against the new variants and could be applicable to other types of COVID-19 vaccines.
