Three Reading scientists provide expert comment on the publication today of the first peer-reviewed study into Phase III trials of a vaccine for the coronavirus.

Dr Simon Clarke, Associate Professor in Cellular Microbiology, University of Reading, said:

“The report on the successful trial of the Oxford/AstraZeneca presents regulators with something of a dilemma. Data are most compelling for the cohort who got half a dose of the vaccine in their first jab. Not only does this seem to confer greater protection against disease, it is in this group that there is a reduction in asymptomatic transmission of the virus, something which is essential if herd immunity is to be obtained to get wider protection of the population.

‘If the regulators allowed the vaccine to be used in this manner, the most at risk group may not be protected’

“Unfortunately, this cohort was relatively small, reducing the reliability of the findings – moreover it did not contain any older participants (age 55 or over) and it remains possible that if the regulators allowed the vaccine to be used in this manner, the most at risk group may not be protected. The researchers have already indicated that further trials may be needed to determine whether this way of administering the vaccine is indeed effective.”

Dr Alexander Edwards, Associate Professor in Biomedical Technology, Reading School of Pharmacy, University of Reading, said:

“The vaccine is clearly safe, and has been into very large numbers of trial participants without any problems. It clearly provides protection that exceed expectations when the trials were planned.

“One question that arose from the initial press release surrounds a different dose used at an early stage- with a “half dose better than full dose” headline- this study now reports in more detail the numbers behind those headlines and terms these groups “SD/SD” and “LD/SD”. The dose and manufacturing batch information is explained fairly clearly in the supplementary information provided with the manuscript along with a great deal of trial details, and we must applaud and celebrate this transparency in sharing everything openly, including explaining that an initial batch had a different than expected dose (the LD/SD protocol).

‘I remain reassured that vaccination programs have finally started us on a welcome path to recovery.’

“Within this, a lot of detail is provided around exactly how you measure and analyse the vaccine dose before putting it in a vial for use. This is a well-studied and well-known area in the field of vaccine manufacturing. Although at first sight you’d think you can just “count the virus particles”, what is produced when this type of vaccine is manufactured and purified is actually a mix of particles, and they can be measured in at least three ways: the amount of nucleic acid determined spectroscopically, the number of copies of viral RNA, and the number of infectious particles. There is nothing alarming or unusual about this but it is a real challenge; this is why vaccine manufacturing is tightly regulated and requires very specialised factories and expert bioprocess engineers. The world has never been better at manufacturing complex biological medicines- we have better than ever tools and equipment. This is also why innovation in vaccines remains vital- to develop vaccines that are easier to produce, ideally less complex and ideally chemically synthesised rather than ‘grown’. But often, the biologically complex vaccines just work better than simpler compositions- this is what our immune system evolved to recognise.

“What is surprising is that a small difference in composition would have any effect on the vaccine protection. The dose was chosen as having the optimal immune response in previous studies, but lower doses also produced similar immune responses in earlier studies. There isn’t a well-known immunological mechanism that would predict that “less is more”.

“However, this apparent difference in effectiveness between different batches will now certainly be a major focus, to make sure that we can make best use of this type of vaccine. We eagerly await further trial data from all ongoing vaccine trials including this one- over time the picture should become clearer. The “dose question” may be a distraction from the main findings of an effective vaccine that meets the target protection, and as a positive person my glass is half-full and the half-dose result will help us to better understand the best use of such vaccines. I remain reassured that vaccination programs have finally started us on a welcome path to recovery.

Prof Ian Jones, Professor of Virology, University of Reading, said:

“The data released today add a lot of flesh to the bones of the earlier press release. AZD1222 is undoubtedly safe and is also capable of preventing disease, so its general roll out would impact the epidemic. Its cost and availability are also powerful positives. But further trial data might be needed to explain why the lower dose group was significantly better protected than the standard dose group, not least as this is not what was reported for the phase 2/3 trial published in November.

‘I would expect the vaccine to be approved and to play its part in bringing the pandemic to a close’

“The number of viruses used in these doses is so high that a two-fold difference would not normally be expected to cause such a difference so it’s possible that something else, manufacturer or batch perhaps, could have played a role. Immunological measures, once completed, may shed some light on this. Subject to the dose or batch issue being resolved I would expect the vaccine to be approved and to play its part in bringing the pandemic to a close.”