Updates on the Oxford, AstraZeneca COVID-19 Vaccine
Reporter: Stephen J. Williams, PhD
AstraZeneca’s potential coronavirus vaccine is likely to provide protection against contracting Covid-19 for about a year, the company’s chief executive told a Belgian radio station on Tuesday.
The British drugmaker has already begun human trials of the vaccine developed by the University of Oxford, with a phase I trial in Britain due to end soon and a phase III trial already begun, Pascal Soriot told broadcaster Bel RTL.
“We think that it will protect for about a year,” Soriot said.
AstraZeneca said on Saturday that it had signed contracts with France, Germany, Italy and the Netherlands to supply the European Union with up to 400 million doses of the potential vaccine.
It has also agreed deals with Britain and the United States.
“If all goes well, we will have the results of the clinical trials in August/September. We are manufacturing in parallel. We will be ready to deliver from October if all goes well,” Soriot said.
From In The Pipeline (Derek Lowe’s regular column in Science)
Criticism of the Oxford Coronavirus Vaccine
By Derek Lowe 18 May, 2020
This piece at Forbes by Bill Haseltine has set off a lot of comment – it’s a look at the Oxford group’s vaccine candidate as compared to the SinoVac candidate, and you may recall (background here) that these are the two teams that have separately reported that their vaccines appear to protect rhesus monkeys from infection after exposure to the coronavirus. Haseltine has some criticisms of the Oxford data, and as you will see from that link to his name, his opinions deserve to be taken seriously. So what’s going on? Update: here’s the take on this at BioCentury.
Looking at the preprint on the Oxford results, Haseltine has a problem with the claim that the monkeys were protected from infection by a dose of ChAdOx1 nCoV-19. The key data are in the preprint’s Figure 3. The Oxford team checked for viral RNA several different ways. One was using bronchoaveolar lavage (BAL fluid), a sampling technique that involves running a bronchoscope down into the lungs and washing out aveolar spaces – a pretty darn invasive assay, which is why you don’t hear about it all that much compared to the still-not-so-nonivasive nose swabs. BAL fluid of the virus-exposed unvaccinated animals showed coronavirus genomic RNA throughout the study, and viral subgenomic RNA (more indicative of active replication) at days 3 and 5 after exposure. Meanwhile, the vaccinated animals showed the genomic RNA in only two monkeys, and no subgenomic RNA at all.
So far, so good. But both vaccinated and unvaccinated monkeys showed the same amount of viral genomic RNA from nose swab samples (Figure 3c). That’s the test that’s used out in the human population, and that means that the vaccinated animals would still be declared as positive for the coronavirus after being exposed to it. And the other thing that Haseltine notes is that the amount (the “titer”, in the lingo) of neutralizing antibodies in the blood of the vaccinated animals does not appear to be that high. You’d like to be able to dilute the blood antibody samples down by hundreds of times or even a thousandfold and still see antiviral activity in an in vitro assay, but in the Oxford case the activity started disappearing at about fortyfold dilution (Figure 2b).
On the positive side, 2/3 of the unvaccinated animals showed clear evidence of viral pneumonia at autopsy, but none of the vaccinated ones did. The conclusion is that the vaccinated animals were indeed infected – the vaccine did not protect against that – but that the disease was definitely less severe. But these results mean that the virus might well still be transmissible from people who had been so vaccinated, even if the disease course itself was not as deadly. You’d want to do better than that, if you can. Haseltine’s take is “Time will tell if this is the best approach. I wouldn’t bet on it.”
Haseltine compares these results to the SinoVac inactivated virus vaccine, and finds that that one looks better – at its highest dose, no viral RNA was recovered from the tissues of the vaccinated animals, for example. This sort of “sterilizing immunity” is what you’d want to aim for – it gives the virus nowhere to go in the human population if you can vaccinate enough people. But it’s worth noting that the SinoVac results were from three doses of their vaccine (versus one of the Oxford candidate), and the viral exposure challenge was about half as strong (total viral particles) as what the Oxford paper used. The Oxford group also inoculated their monkeys in both the upper and lower respiratory tract, while the SinoVac team used a single inoculation in the trachea. So I agree with that tweet linked from AndyBiotech; I don’t think that a head-to-head comparison is fair. But Haseltine’s point stands, that the results as we have them from the ChAdOx1 nCoV-19 vaccine did not actually protect monkeys from infection.
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