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Many scientists scratch their heads trying to explain the encouraging but rather unusual results of clinical trials by the University of Oxford and the British company AstraZeneca, which show that it is more effective (up to 90%) when the first of its two doses is taken. administered in half. Contrary to what might be expected, when the first dose was given in its entirety, the efficacy of the vaccine in the trials appeared to be considerably lower (only 62%).
As the preliminary results of the phase 3 clinical trial showed, the vaccine showed an average efficacy of 70%, two weeks after the second dose. The two doses were administered one month apart, and efficacy was related to the likelihood that those vaccinated with Covid-19 would become ill compared to those who had received placebo.
Several scientists, as reported by “Nature”, have pointed out that it is not possible to make a direct comparison with the other vaccines (Pfizer / BioNTech and Moderna), which have shown up to 95% effectiveness in tests, since the data available up to the timing are insufficient. . Among other things, it was not known how many participants in the Oxford / Astra Zeneca trials were actually vaccinated and how many were pseudovaccinated.
“90% is enough, but 62% for the second vaccination regimen (two full doses) is not that impressive,” said Florian Kramer, a virologist at Mount Sinai School of Medicine in New York.
“We have a slight risk of comparing apples to oranges. We still have a long way to go before the data is clarified and fully published,” said immunologist Daniel Altman of Imperial College London.
The British vaccine of different technology is based on a modified common cold adenovirus, isolated from chimpanzees, that no longer reproduces in human cells. The vaccine directs cells to produce the protruding spike protein with which the SARS-CoV-2 coronavirus penetrates and infects them. Protein production artificially activates the body’s antibodies, creating immunity.
Final phase 3 clinical trials of the vaccine had started earlier than those of Pfizer / BioNTech and Moderna, but they were the first to anticipate and publish the extremely encouraging interim results of their trials. Trials of the Oxford / AstraZeneca vaccine are ongoing in several countries (USA, Russia, Japan, South Africa, etc.). The interim results were based on 131 cases of Covid-19 diagnosed among more than 11,000 volunteers who participated in the trials in Britain and Brazil.
Possible explanations
The key challenge for scientists is understanding how the vaccine can be so effective at a lower dose. One possible explanation, according to virologist Luke Vadenberge of Harvard University School of Medicine, is the statistics: The vaccine trial was not large enough to accurately measure the difference in efficacy between the two vaccine regimens ( half and the first full dose). ). Therefore, the “scissors” will likely disappear when more cases of Covid-19 disease come to light among the participating volunteers.
The estimate of the high efficacy of the “half the first dose and the second full dose” regimen was based on data analysis of only 2,741 subjects, whereas the lower efficacy of the “two full dose” regimen was based in 8,895 volunteers. Epidemiological statistician Stephen Evans of the London School of Health and Tropical Medicine estimates that, in fact, the first half of the dosing regimen may not be more than 66% effective.
“We believe that with the smallest first dose, we stimulate the immune system differently, helping it respond better,” said Dr. Andrew Pollard, director of the Oxford Vaccine Group. In single-dose vaccines, as he said, the rule is that the higher dose brings better results, but in two-dose vaccines the first dose activates the immune system and the second stimulates it even more.
“I don’t think this is an anomaly,” said Katie Euger, an immunologist at the Jenner Institute in Oxford who is also involved in the development of the vaccine. He believes that the unexpectedly higher efficacy of the lower dose is due to the fact that the lower dose better activates T cells that support antibody production, or the fact that the vaccine triggers an immune response not just to the coronavirus protein but also coronavirus. in the components of their transport “vehicle”, that is, the modified chimpanzee adenovirus. For some unknown reason, the first full dose is supposed to prevent this complete immune response.
A “reasonable explanation” was given by virologist James Wilson of the University of Pennsylvania, who pioneered the use of adenovirus in vaccines in the 1990s. Adenovirus vaccination in rodents: that, in a two-dose vaccine, one Low first dose may lead to better immune protection than higher first dose. This is probably because the first small dose leads to more rapid formation of “memory” cells after the second dose, an effect that he estimates can also be achieved if the time between two full doses is longer.
AstraZeneca intends to collect more data on the dose-effectiveness relationship. However, scientists believe the company is more likely to eventually seek permission from supervisory authorities for the regimen with the lowest first dose.
“It would be foolish to use more vaccines than necessary to ultimately be less effective,” Dr. Wuger said.
In any case, independent scientists consider positive evidence for the British vaccine that none of the trial participants who became ill with coronavirus had the severe form of Covid-19, nor did they require hospitalization. There is also evidence that the vaccine can prevent vaccinated people from transmitting the virus, even if they become infected or are asymptomatic. According to Iweer, the vaccine appears to block transmission of the coronavirus, something for which there is no evidence for other vaccines so far.
In addition, beyond the question mark for its effectiveness, the British vaccine is cheaper and easier to use in practice, since it is stable at a simple refrigerator temperature, without the need for special freezers.
SOURCE: ΑΠΕ – ΜΠΕ
