The Oxford-AstraZeneca Covid-19 vaccine appears to substantially reduce transmission of the virus, rather than simply preventing symptomatic infections, UK researchers have suggested.
The rate of positive PCR tests declined by about half after two doses, according to preliminary results by researchers at the University of Oxford that have yet to be peer reviewed.
Their analysis, released as a preprint Tuesday, also supports spacing out doses and estimates good efficacy after just one shot of the Oxford-AstraZeneca vaccine.
The study did not measure transmission directly -- for example, by tracing contacts who were infected by study volunteers. But the researchers did collect regular nasal swabs from some participants and found that the rate of positive PCR tests fell by half after two doses of the vaccine. After one dose only, the rate of positive tests fell by 67%.
'While transmission studies per se were not included in the analysis, swabs were obtained from volunteers every week in the UK study, regardless of symptoms, to allow assessment of the overall impact of the vaccine on risk of infection and thus a surrogate for potential onward transmission,' the authors write.
If the vaccine were simply making infections milder, PCR positivity would not change, the authors argued in the preprint analysis. 'A measure of overall PCR positivity is appropriate to assess whether there is a reduction in the burden of infection.'
Coronavirus vaccine trials have primarily looked at prevention of symptomatic cases of Covid-19. Previously, there has been little other public data suggesting that vaccines could prevent people from passing the infection to others.
Speaking to the UK's Science Media Centre (SMC), Helen Fletcher, professor of immunology at the London School of Hygiene and Tropical Medicine, said the data in the study 'suggest a possibility that the vaccine could have an impact on transmission but further follow-up would be needed to confirm this.'
Dr. Doug Brown, chief executive of the British Society for Immunology, told the SMC the study 'hints that the Oxford/AstraZeneca vaccine may be effective in stopping people being able to transmit the virus.'
He added: 'While this would be extremely welcome news, we do need more data before this can be confirmed and so it's important that we all still continue to follow social distancing guidance after we have been vaccinated.'
Salim Abdool Karim, the chair of the South African government's coronavirus advisory panel, told CNN on Wednesday that the results shared in the preprint were a 'promising start' to understanding coronavirus transmission after vaccination but that more research is needed.
The vaccine showed 66.7% efficacy against symptomatic disease starting two weeks after the second shot, researchers at the University of Oxford said.
The new analysis adds new trial sites and a month of new data to the mix, building upon earlier results announced by AstraZeneca that its vaccine had showed an estimated 70.4% efficacy.
However, the latest research also suggests the vaccine may offer substantial protection after a single shot.
The study estimates 76% efficacy up to three months following one dose. This is based on a subset of 88 symptomatic infections, split unevenly between the vaccine and placebo groups between 22 and 90 days after vaccination. The study also found relatively stable levels of antibodies during this time frame, 'with minimal waning by day 90.'
Furthermore, the authors suggest there could be higher efficacy with more spaced-out doses. Among adults age 18 to 55, vaccine efficacy appeared to rise when the time between shots was spaced out from less than six weeks to more than 12. However, more information is needed to know how statistically different that finding is.
Taken together, the findings may bolster the UK's decision to recommend spacing out doses up to 12 weeks apart, according to a statement from the chief investigator of the Oxford Vaccine Trial and co-author of the paper, Andrew Pollard.
'This is positive news as it shows that just one dose of this vaccine generates good levels of immunity and that this protection does not seem to wane in the shorter term,' said Brown, of the British Society for Immunology.
'In immunology terms, this finding is not unexpected as we know that some other vaccines confer better immunity when the doses are more spread out. Although further information is required to confirm these findings for older age groups, overall this new research should provide reassurance around the UK's decision to offer the two doses of this vaccine 12 weeks apart.'
Professor Azra Ghani, chair in infectious disease epidemiology at Imperial College London, cautioned against interpreting the estimates in the study as indicative of a higher efficacy with a longer dosing gap, citing limitations with the study design.
'Most importantly, the study was not designed to look at different dosing gaps or at one versus two doses. This means that participants weren't randomised and it is therefore quite possible that there are other things that are driving this apparent trend with dosing schedule,' she told the SMC.
'The only way in which this question can be answered robustly is in a prospective trial with different dosing schedules compared side-by-side.'
Stephen Evans, professor of pharmacoepidemiology at the London School of Hygiene and Tropical Medicine, said the extra data in the paper were helpful but that some 'inevitable uncertainty' around exact efficacy values remained.
'The data definitely provide some evidence to suggest that the eventual protection from two doses of this vaccine are not worsened by having a longer than 28 or 42 day period between doses and tend to confirm what had been shown before, that if anything the eventual efficacy was better,' he said. 'The data also do not provide any evidence that efficacy wanes after the first dose.'
Similar data is not yet available on delaying the second dose of the Pfizer/BioNTech vaccine to 12 weeks after the first dose, said Dr. Gillies O'Bryan-Tear, past chair of policy and communications at the Faculty of Pharmaceutical Medicine in comments to the SMC. But, he added, 'most commentators agree that it is likely to be the same with that vaccine, and indeed, other two dose vaccines.'
The authors caveat that the trials were not initially designed to evaluate efficacy by dose intervals, but the data 'arose due to the logistics of running large-scale clinical trials in a pandemic setting.'
The primary analysis is based on 332 symptomatic infections that occurred among more than 17,000 trial volunteers in the UK, Brazil and South Africa more than two weeks after their second dose.
AstraZeneca announced last month it had completed enrollment in its Phase 3 trial in the United States, which will serve as 'the primary basis' for the company's eventual application to the US Food and Drug Administration.
The vaccine has already been authorized in a number countries, such as the UK and India, but authorization may not come in the US until late March at the earliest, according to Operation Warp Speed's Moncef Slaoui.