Two doses of the AstraZeneca vaccine administered 44-45 weeks apart generated nearly four times the level of antibodies than when the doses were given 8-12 weeks apart, says a report by the Oxford Vaccine Group, the developers of the vaccine, on Monday. Antibody levels remained elevated for nearly a year and a third booster dose of the vaccine, given to a subset of volunteers, also significantly boosted antibody levels to twice that after a second dose.
“A single dose of ChAdOx1 nCoV-19, with a second dose given after a prolonged period, may, therefore, be an effective strategy when vaccine supplies are scarce in the short term. A third dose results in a further increase in immune responses, including greater neutralisation of variant SARS-CoV-2 viruses, and could be used to increase vaccine efficacy against variants in vulnerable populations,” the authors report in a pre-print publication. This means the study is yet to peer-reviewed.
A group of vaccine volunteers who got their second dose 15-25 weeks after the first, saw average antibody levels at nearly twice those in the 8-12 week interval, suggesting that lengthening the duration between doses appeared to be boosting antibody count.
Thus, average IgG (immunoglobulin G) levels for 8-12, 15-25, and 44-46 weeks were 923, 1860 and 3738 units respectively, when measured 28 days after the second dose. The volunteers chosen were among those who'd been part of the phase 1/2 and phase 2/3 clinical trials.
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Covishield, which is the India-made version of the AstraZeneca vaccine, is now the mainstay of India's vaccination programme comprising nearly 88% of the 32 crore doses administered so far. Though the dosage interval of the vaccine was initially designed as between 4-6 weeks, a supply crunch in May, as well United Kingdom data on the vaccine’s efficacy administered 8-12 weeks apart weighed on Indian experts to recommend a 12-16 week interval between two doses of the vaccine.
The latest study also reported reduced common adverse events after the second dose compared to the first. After a first dose, antibody levels peaked in 28 days and after 180 days were nearly half as that of the peak. At 320 days, these were only 30% of the peak levels.
However protection against symptomatic disease is a result of the combined action of vaccine induced antibodies and cellular immunity, or T cell immunity, experts have noted, though it isn't known how much of each is required to guarantee complete protection.
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A group of scientists, many affiliated to the Oxford Vaccine Group have previously shown that protection against symptomatic COVID-19 from 22 days after the first dose was around 76% and a second dose administered 12 weeks after the first, improved it to 81%.
In the case of the Pfizer vaccine, a single dose conferred protection of 52% whereas it increased to 95% after the second dose. An analysis from the British Covid-19 infection survey found that both the Pfizer and AstraZeneca vaccines reduced infections by 61%-66% after the first dose and 80%-79% after the second dose. “A second dose is needed to fully develop the immune response,” said Shahid Jameel, Director, Trivedi School of Biosciences, Ashoka University, who perused the newest paper.
Also read: Covishield protects against double mutant: study
The study also reported higher antibody levels after the second dose than prior to it when antibody levels were measured against the coronavirus variants Alpha (B.1.1.7), Beta (B.1.351) and Delta (B.1.617.2), also the most prevalent variant in India.
Professor Sir Andrew Pollard, Professor of Paediatric Infection and Immunity and Lead Investigator of the Oxford University trial of the vaccine, said in a statement, “This should come as reassuring news to countries with lower supplies of the vaccine, who may be concerned about delays in providing second doses to their populations. There is an excellent response to a second dose, even after a 10-month delay from the first.”
Epidemiologist and public health expert Chandrakant Lahariya told The Hindu that the new findings reinforced what was known — that a longer gap, between doses was effective. That a third dose was safe and provided higher antibody levels than a second dose implied that the vaccines would likely continue to be effective against variants.
“We still don’t have a definite measure of minimum antibody levels required for protection and so higher antibody levels are likely to be more protective against variants. What’s reassuring also is that the vector used to make the vaccine (a non-replicating chimpanzee virus) is able to generate antibodies after the third dose.”
