Vaccine combination, the future of the fight against the coronavirus?

The results announced in an article published in the Lancet report that mixed programs -of which Pfizer-BioNTech followed by Oxford-AstraZeneca and Oxford-AstraZeneca followed by Pfizer-BioNTech- induced high concentrations of antibodies to the peak IgG protein of SARS-CoV2 when the doses were given four weeks apart. Which suggests that the combination sometimes exceeds two injections of the same vaccine, and a similar picture emerges from German studies.

Professor Matthew Snape, associate professor of pediatrics and immunization at the University of Oxford and principal investigator of the trial, said: “The Com-COV study evaluated mixed alternatives to the Oxford and Pfizer vaccines to see in to which extent they can be used interchangeably, potentially allowing flexibility in the UK and worldwide deployment of assays. The results show that When given four weeks apart, the two mixed regimens induce an immune response above the threshold established by the standard Oxford / AstraZeneca vaccination schedule. Notably, the order of the vaccines made the difference, with an Oxford-AstraZeneca / Pfizer-BioNTech program inducing higher antibodies and T cell responses than Pfizer-BioNTech / Oxford-AstraZeneca, and both inducing higher antibodies than Pfizer-BioNTech / Oxford-AstraZeneca. those of the permitted standards, and a two-dose Oxford-AstraZeneca program is very effective. The highest antibody response was observed after the two-dose schedule of Pfizer-BioNTech, and the highest T-cell response from Oxford-AstraZeneca followed by Pfizer-BioNTech. “

Snape said that “these results are an invaluable guide to using mixed dose schedules; however, the four week interval studied here is shorter than the eight to 12 week schedule most commonly used for the Oxford-AstraZeneca vaccine. if you know that this longer interval results in a better immune response, and results for a 12-week interval will be available shortly. “

The next scenario

The COVID-19 vaccine combination is shaping up to be a good way to give people the protection they need when faced with unpredictable supply and security challenges.. People can now “feel a little more comfortable with the idea of ​​mixing and matching.”», Explains immunologist Leif Erik Sander at Charité University Hospital in Berlin.

The results also give researchers assurance that the combination of other COVID-19 vaccines, that haven’t been tested together yet, that might work too. Although at least 16 vaccines have already been approved in one or more countries, and the studies combined so far have been small.

The latest analyzes were prompted by concerns about the safety of the vaccine developed by the University of Oxford and the pharmaceutical company AstraZeneca in Cambridge, both in the UK. The application has been associated with rare cases of a blood clotting disorder known as thrombosis with thrombocytopenia, and in March, some European countries decided to suspend its use in certain groups of people. This has left many people partially vaccinated, unless they switch to a different brand for their second dose.

In May, researchers from the Carlos III Health Institute in Madrid announced the results of the CombiVacS trial . The study found a strong immune response in people who received the vaccine developed by pharmaceutical company Pfizer, based in New York, and biotechnology company BioNTech in Mainz, Germany, 8 to 12 weeks after receiving a dose of Oxford-AstraZeneca vaccine.

There was no direct comparison with people who received two doses of the same vaccine, but the authors found that, in laboratory tests, those who received the combination produced 37 times more neutralizing antibodies SARS-CoV-2 and 4 times more SARS. CoV-2-specific immune cells, called T cells, than people who have received a single dose of Oxford-AstraZeneca Injection.

By the end of June, other results had emerged showing a similar effect. Sander and his colleagues examined 340 healthcare workers who had received two doses of the Pfizer-BioNTech vaccine or an initial injection of the Oxford-AstraZeneca vaccine followed by one dose of Pfizer-BioNTech. Both patterns elicited an immune response that included neutralizing antibodies and T cells.

A third study, conducted by researchers at the University of the Saar in Homburg, Germany, found that the mixed diet was more effective in triggering an immune response than two injections of Oxford-AstraZeneca. It was as good or better than two shots of Pfizer – BioNTech.

Just a few weeks ago, the team behind the UK trial, known as the Com-COV study, posted a preprint online showing it had been obtained. a good immune response regardless of the order in which the two vaccines were administered.

However, trials so far have been too small to test the effectiveness of vaccine combinations in preventing people from developing COVID-19. “As long as you don’t have long-term or follow-up studies with efficacy estimates, it’s hard to tell the level or duration of protection,” says Martina Sester, the immunologist who led the study of the Saarland.

Another limitation of the work so far is that there is no easy way to compare different combinations between studies. “Large-scale efficacy studies are increasingly difficult,” says Sester. This is because as infection rates decline, the number of people in a study must increase to detect any difference in the extent of disease. “Trials facing combination and combination vaccine sequences with placebo control would also be unethical.”he adds.

This is one of the reasons that efforts are being made to determine a “correlate protection “: A defined level of immune response that provides protection against infection and disease. “It’s extremely urgent,” says Sander.

Until, no mixed trials reported serious side effects. In the Com-COV study, mixing the vaccines caused more side effects than giving two doses of the same vaccine, according to preliminary data. But this was not the case in the Charité and Sarre or CombiVacS studies, where the side effects were not worse than with two injections of the same vaccine.

“This is probably due to the interval between doses.”Sester guess. The Com-COV participants discussed in the last article received their second injection four weeks after the initial dose, while German study participants had at least nine weeks between injections. Some Com-COV participants received doses at a longer interval.

“Some security concerns remain -continue Sander-. Two different vaccines are combined, which may have their own profile of events and side effects, which could amplify the problems.”.

So far, studies have only recruited a few hundred people. This means that are too small to detect rare events such as coagulation conditions, which are currently estimated to occur in approximately one in 50,000 people after the first dose of Oxford-AstraZeneca vaccine and in less than one in 1.7 million people after the second application. The disease has also been linked to an adenovirus vaccine produced by the pharmaceutical company Johnson & Johnson in New Brunswick, New Jersey. In small studies, “you miss your side effect one in 1,000, not to mention one in 50,000,” said Matthew Snape, an Oxford vaccine researcher who is leading the Com-COV study, during a press conference on June 28th.

The lingering possibility of rare side effects is one reason some researchers recommend that people stick to the standard two injections of a single vaccine at this time. “In my opinion, it’s best to default to what we know it works for and there is a known amount when it comes to their security,” Snape concludes.

But as new variants of SARS-CoV-2 emerge, the results of mixed trials could provide policymakers with the data they need to switch to more protective combinations. “If there is a global shortage of a particular vaccine, then instead of stopping the immunization program, you can continue,” Russell said. Meanwhile, Snape goes out of his way to take care of him at all costs.

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