Sputnik V: new pre-print, new concerns.

Introduction.

A new preprint has been recently released, claiming that two doses of the Sputnik V vaccine can elicit a stabler antibody response against Omicron compared to 2 doses of the Pfizer/Biontech vaccine.

In the preprint, 51 samples from 17 individuals vaccinated with two Pfizer/Biontech vaccine doses are compared to 31 samples obtained from 31 individuals immunised with the Sputnik V vaccine.

After examining the decay of the neutralising antibody titre at different time points, the crucial conclusion from the authors is the following:

“The decrease in neutralizing antibody (NtAb) to the Omicron variant was 8.1 folds for group of Sputnik V-vaccinated and 21.4 folds for group of BNT162b2-vaccinated. Analysis showed that 74.2% of Sputnik V- and 56.9% of BNT162b2-vaccinated sera had detectable NtAb to SARS-CoV-2 Omicron variant.”

In the following, I will show why this conclusion is simply not supported by the presented data and the study design is wrong.

Analysis of the preprint: crucial issues.

Let’s first consider the data presented in figure 1A, reproduced below.

This figure is used to say that there are no statistically significant differences between the RBD-specific IgG and the NtAb titre in two groups of serum samples, i.e. 31 samples obtained from individuals fully vaccinated with Sputnik V from no more than six months, and 51 samples obtained from individuals vaccinated with Pfizer/BionTech from no more than six months.

However, there is an important drawback, rendering the statistical comparison between the two groups completely meaningless.

In the preprint, the authors themselves state the following:

“The median and IQR of time after the second dose of the vaccine was 91 days (56-122) for Sputnik V and 90 days (14-180) for BNT162b2”.

This indicates that in the Pfizer/Biontech group, there are samples which, on average, are more distant in time from the second dose than in the Sputnik V group. In turn, this implies that the comparison among the two groups is biased toward a more pronounced decay of NAbT in the Pfizer group than if you select two appropriately matched groups.

Moreover, while you have a continuous distribution in time for the Sputnik samples, the Pfizer/Biontech samples correspond to a discrete distribution, since they are aged precisely 0 weeks (first 17 samples), three months (second 17 samples) and six months (last 17 samples). Now, you cannot statistically compare the way the authors do a single batch of samples from 31 individuals, vaccinated at different times, with 3 batch of samples coming from the same 17 individuals.

It should be more than enough to prevent any further discussion contrasting the two groups; however, let’s follow the authors and go on with the analysis.

To compare the NtAb titre decay in the two analysed populations, the authors assess their concentration at different time points, as shown in Figure 1, panels C) and D) of the preprint, reproduced below.

Now please look at the time points, i.e. the quantities circled in red. 15 Sputnik samples are from a period “up to 3 months” after the second dose; however, if you look for a comparator in the Pfizer/Biontech group, we found 17 samples, all from 3 months after the second dose. The same is true for the second time point: we have 16 Sputnik samples from “3-6 months” after the second dose and 17 samples, all from 6 months after the second dose for the Pfizer/Biontech group.

This confirms once more that the Pfizer/Biontech samples are systematically older than the Sputnik ones; it should surprise us, that their NtAB titres are on average lower.

Thus, a direct comparison between the data presented in figure 1C and 1D is grossly misleading and methodologically wrong; but the authors, apparently unaware, wrote:
“In general, Omicron-specific NtAbs were detected in the blood sera of 74.2% of the Sputnik V-vaccinated, and 56.9% of the BNT162b2-vaccinated (Figure 1C, 1D).”

This and other similar statements then leaked to the international press, promoting the fake idea that such data prove the superiority of one product over the other.

More problems.

The issues above render the presented study misleading and its claims unsupported; however, there are further elements to be recalled.

First, the “absence of data about age-dependent and comorbidity-dependent NtAb response” (as per the authors’ words) renders impossible a correct match between the groups of individuals enrolled in the study, so that important confounding factors are left unaddressed.

Second, it is not clear which was the source of the Sputnik samples, who performed the analysis and where. This is not only a legal issue – this sort of material is carefully monitored when travelling from one country to another – but also a methodological one: were all the samples treated in the same way by the same team, and if so were the experimenters blind to the identity of the samples?

Third, nothing in the presented study can be used to mantain that “the most effective approach, already shown in several studies, is the use of heterologous booster vaccination pioneered in COVID-19 vaccines by Sputnik V”, as the authors write in their conclusions. The preprint discuss a double dose of Sputnik versus a double dose of Pifizer/Biontech vaccine; so the geopolitical marketing currently undergoing to promote this concept is unwarranted and at best premature.

Fourth and last, there is a problem connected to the funding of the presented preprint. The original preprint clearly states that the Russian fund RDIF funded the study.

However, the current clinical director of the INMI Lazzaro Spallanzani, and author of the study, Francesco Vaia, apparently declared this was not the case. This is relevant, because the RDIF fund is also the owner of the Sputnik patents and the main sponsor of the Russian vaccine. So, which is true? And if no Russian money was involved, how this study was funded, and when its funding was approved? By whom?

Final considerations.

It is very unfortunate that, when it comes to science, the data presented in support of the Sputnik V, as well as the methodologies and the conclusions, are as usual not sufficient to support the claims.

It is also unfortunate that on the basis of such misleading evidence and missing checks, misinformation is so easily spread; researchers and scientific institutions should stick to science, instead of entertaining the press with wrong notions on the premise of a preprint like this one.

We are still waiting for the data supporting the various papers that appeared on the Lancet; I don’t have much hope that someone will address these further concerns on the work performed by the Gamaleya and the Spallanzani researchers, but, at least, I hope anyone could consider in the proper light the results presented in this last preprint.