Efficacy of Oxford–AstraZeneca COVID-19 (CoviShield) vaccine
There has been a lot of confusion regarding the efficacy of the CoviShield vaccine and it’s relation to the gap between the two doses. Indian government has changed the recommended gap between the doses 3 times till now (4 weeks, 6–8 weeks and recently 12–16 weeks) citing “real-life” evidence especially from the UK. Interestingly, just a day after this decision, UK decreased the gap from 12 weeks to 8 weeks based on the concerns that the ‘Indian’ variant is more infectious and the need to protect their population quickly.
The Indian government’s decision has left many people wondering (especially those who have already recieved the vaccines with a gap less than 12 weeks) what ideally should be the gap between the two doses.
This article aims to bring the information present regarding the efficacy and the gaps in one place. I am not an expert on the topis and thus will try to stick to the research without providing any opinions.
What is the Oxford-AstraZeneca vaccine?
AstraZeneca COVID-19 Vaccine (Code: AZD1222) is a viral vector vaccine, which means the genetic code of the spike protien (DNA, in this case) is added to another virus called an adenovirus. Adenoviruses are common viruses that typically cause colds or flu-like symptoms. The Oxford-AstraZeneca team used a modified version of a chimpanzee adenovirus, known as ChAdOx1. It can enter cells, but it can’t replicate inside them [1].
Study 1: Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK
The first trial was conducted by AstraZeneca and Oxford and they published their findings on 8th December [2].
These are the results:
LD/SD: The priming dose (first dose) was a “low dose” whereas the booster dose (second dose) was a “standard dose”.
SD/SD: Both the doses were “standard dose”.
Gap between the two doses in the study
Interestingly, in this trial the researchers were not able to moderate the gap between the two doses. The gap varied across the groups and the above findings include people who recieved the vaccine with a gap varying from 4 to 12 weeks. The authors mention “The timing of priming and booster vaccine administration varied between studies. As protocol amendments to add a booster dose took place when the trials were underway, and owing to the time taken to manufacture and release a new batch of vaccine, doses could not be administered at a 4-week interval.”, in the paper
Study 2: Single-dose administration and the influence of the timing of the booster dose on immunogenicity and efficacy of ChAdOx1 nCoV-19 (AZD1222) vaccine: a pooled analysis of four randomised trials
The (almost) same group of people published another study [3] on 19th Feb talking about the influence of the gap on the immunogenecity of the vaccine.
Findings: “In the participants who received two standard doses, after the second dose, efficacy was higher in those with a longer prime-boost interval (vaccine efficacy 81·3% [95% CI 60·3–91·2] at ≥12 weeks) than in those with a short interval (vaccine efficacy 55·1% [33·0–69·9] at <6 weeks). These observations are supported by immunogenicity data that showed binding antibody responses more than two-fold higher after an interval of 12 or more weeks compared with an interval of less than 6 weeks in those who were aged 18–55 years.”
Results:
Vaccine Efficacy vs Interval for SD/SD group:
Vaccine Efficacy vs Interval for LD/SD group:
“Each datapoint shows one estimate of vaccine efficacy calculated in a subset of participants who received two doses of vaccine with a prime-boost interval falling within a 20-day interval. The x-axis shows the midpoint of the interval such that the first datapoint”. So in the above plots, the efficacy reported at interval of 36 is calculated from a sample of group who recieved the vaccine with a gap of 26–46 days.
What now?
So, it does seem like the increasing the gap increases the efficacy of the Oxford-AstraZeneca vaccine. Given this result, it is natural to wonder then why the government had started the vaccination of high-risk group with a short gap of 28 days. It is unclear that why the government has changed the recommended gap now when the evidence for increased efficacy has been since Februray, if not before. According to [4], Indian government had decided to go ahead with the shorter gap citing that the scale of India’s vaccination drive had necessitated it.
Regarding the decisin to increase the gap, the government says this decision is based on scientific evidence [5] “When you are in a very difficult situation, the way you are in India, you have to try and figure out ways to get as many people vaccinated as quickly as you can, so I believe that it is a reasonable approach to do,” Antony Fauci said on the government’s decision on increasing the gap.
The decision can not solely be based on the efficacy, there are other factors which influence this decision. The lack of transperancy in government’s decision making and the frequent changes in the guidelines, thus, leaves the people confused and doubtful.
At an individual level too, the decision is not straightforward. One should consider the trade off between a quick but apparently lower immune response and a better but delayed response. Given the spread, every day is very risky if a person is not vaccinated. [6–7] are some general advice which might be helpful in making these decisions.
[1] https://www.nytimes.com/interactive/2020/health/oxford-astrazeneca-covid-19-vaccine.html
[2] https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)00432-3/fulltext
[3] https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)00432-3/fulltext
[4] https://www.theweek.in/health/more/2021/04/23/the-reason-behind-the-longer-gap-between-vaccine-jabs.html
[5] https://www.hindustantimes.com/india-news/saddening-vk-paul-on-claims-that-covishield-dose-gap-widened-owing-to-crunch-101621073799487.html
[6] https://www.hindustantimes.com/india-news/when-to-take-covid-19-vaccine-2nd-dose-when-to-take-1st-dose-if-once-infected-here-s-all-you-need-to-know-101620893941629.html
[7] https://www.youtube.com/watch?v=K3odScka55A
