Scientists from around the world have signed an open letter expressing concern around claims Russia has produced a vaccine that provides some immunity against the coronavirus.
In August, Russian officials were the first to approve a jab after less than two months of human testing. Vladimir Putin announced the vaccine offered “sustainable immunity” against the virus and that one of his daughters has been inoculated.
Experts were initially cynical, however, hopes were slightly raised on 4 September when two “small but encouraging” studies suggested the vaccine was safe and produced an immune response.
While many stressed it was a case of “so far, so good”, a letter spearheaded by Dr Enrico Bucci from Temple University in Philadelphia has since called some of the results “highly unlikely”.
The signees, which numbered 26 by Wednesday evening, acknowledged “the public’s extreme interest and expectations for an effective vaccine”, but added this should “motivate the scientific community to pay even more attention to the evidence”.
Writing in the prestigious medical journal The Lancet, a team of Russian scientists concluded there were no serious safety concerns in 36 volunteers up to 42 days after the vaccine was administered.
It was also found to bring about an immune response in 40 volunteers within 21 days. Many experts were quick to point out, however, the jab’s ability to prevent infection or severe illness “has not yet been shown”.
Some added the results were sufficiently encouraging for the vaccine to be investigated further in larger studies.
Not everyone is convinced, however.
An open letter published on the Italian site Cattivi Scienziati – which promises to “fight bad and pseudo-science” – addresses the Russian scientists and Richard Horton, editor of The Lancet.
The signees – hailing from Milan University to Leeds Teaching Hospitals – have accused the scientists of not providing “numerical data for all the experiments”.
This “would be of great help in evaluating the present study, enabling to directly reproduce all analyses and findings, rather than trying to do so from data abstracted or inferred from the figures”, they wrote.
Based on the “research described in the article”, the signees pointed out “several different points of concern”.
The Russian scientists analysed a frozen and freeze-dried formulation of the vaccine.
Both formulations are based on adapted strains of the adenovirus. This usually causes the common cold but has been modified to express the coronavirus’ spike protein, which it uses to enter cells.
To test the vaccine’s safety as part of a phase 1 trial, four groups of nine healthy volunteers were given either the frozen or freeze-dried jab.
One group received a frozen version of an adenovirus strain called type 26, while another had type five. The remaining two groups were given the freeze-dried formulation of type 26 or type five.
To gauge the formulations’ efficacy in a phase 2 trial, 40 volunteers had either a frozen or freeze-dried type 26 jab, followed by a type five booster three weeks later.
A chart in The Lancet combined the volunteers’ antibody responses following vaccination with the different formulations. Antibodies are proteins produced by the immune system to help fight off an infection.
The signees were sceptical about “several data patterns appearing repeatedly”.
Among the volunteers receiving a frozen version of type 26, all nine appeared to have “identical antibody titres at 21 and 28 days”, they wrote.
This was also true for seven of the nine volunteers given the freeze-dried version of type 5, added the signees.
In other parts of the studies, the volunteers’ antibody levels “differed for a constant value in two completely unrelated experiments”, while the levels were “completely preserved among [an]other two completely unrelated volunteer groups”.
“It seems to us that on the ground of simple probabilistic evaluations, the fact of observing so many data points preserved among different experiments is highly unlikely,” wrote the signees.
They added antibody data for each individual volunteer across the different days would be “highly beneficial in reporting (and hence) interpreting the results”.
Antibodies aside, the results also suggest other aspects of the immune response were “continuous in nature” between different formulations of the vaccine, a “coincidence” the signees called “even less likely”.
“Please note that, in lack of the original numerical data, no conclusions can be definitively drawn on the reliability of the data presented, especially regarding the apparent duplications detected,” they wrote.
Rather than have a placebo group – the gold standard of medical research – the Russian scientists compared their results to the immune response of people who naturally fought off the coronavirus, concluding it “appears to be higher in people vaccinated”.
The signees called this approach a “further concern”.
“The authors did not specify enough characteristics of the convalescent [recovering] patients used as a control,” they wrote.
“How were they matched to the different groups of enrolled volunteers? It is also crucial to know when their plasma was collected – for each patient, how many days passed since symptoms and seronegativization [testing negative for the coronavirus] occurred?
“During the current pandemic, the public extreme interest and expectations for an effective vaccine are fully understandable.
“However, the very same reasons should motivate the scientific community to pay even more attention to the scientific evidence and the underlying data, and it is thus of utmost importance that they are fully available for close scrutiny.”
At the time of the studies’ publication, criticism centred around the trials being too small to accurately gauge safety, as well as uncertainty over whether an antibody response “translates [to] protection in the field”.