New debate: what is the combination of COVID-19 vaccine doses

In front of a visible problem of manufacturing, distribution and logistics for the various vaccines against COVID-19 approved can be applied on the shoulders of billions of people around the world, researchers around the world are testing combinations. Some are in clinical trials, while others are only tested on animals.

In January, UK implemented a change in its vaccine-related guidelines that surprised many health experts: if the second dose of a certain vaccine was not available, patients could receive a different one.

This new rule was based on simple guesswork; At the time, there was no scientific data showing that the mixture of two coronavirus vaccines was safe and effective. But that could change soon.

In this context, Carlos III Health Institute (ISCIII), public research body dependent on the Ministry of Science and Innovation and the Ministry of Health of Spain, will be the promoter of a clinical trial, called CombivacS, which will analyze the possible protective effect and safety of administering a dose of Pfizer to people who have already received a first dose of the vaccine from the AstraZeneca laboratory, after a minimum of 8 weeks has passed since this dose.

As the institute announced in a statement, the clinical trial, which was launched after the suspension of vaccination with AstraZeneca serum in people under the age of 60, seeks to provide scientific evidence to support decision making regarding a possible alternative to full vaccination in these individuals. In other words, the study aims to clarify whether people who received the first dose of AstraZeneca have generated enough antibodies or whether a booster dose with another vaccine is needed.

During clinical vaccine development Pfizer and AstraZeneca Different studies have been developed to define the dose, efficacy, safety and conditions of use of each of them individually.

After approval from health authorities, both have been available for some time and administered in Europe, but, so far, there are no clinical data on their possible combined use. “Joint use seems possible and even desirable”, According to experts from this Spanish institute, “Since these are vaccines that work with different mechanisms of action and this way of treating other diseases has been shown to be beneficial, but clinical trials like this are needed to verify this. “

The CombivacS study is one of the first clinical trials to examine the safety and immunogenicity of this type of combination regimen. It will be developed in five hospitals: La Paz and the San Carlos clinic in Madrid; Vall d’Hebron and Clínic, in Barcelona, ​​and Cruces in Vizcaya. ISCIII’s National Microbiology Center (CNM) will act as the central laboratory for the trial, which has received scientific advice from the Spanish Agency for Medicines and Health Products (AEMPS). AEMPS, after approval of the protocol by the Pharmaceutical Research Ethics Committee (CEIm) of La Paz University Hospital in Madrid, issued the necessary authorizations for its implementation.

In dialogue with Infobae, the renowned doctor Marta Cohen, an Argentinian pediatric pathologist living in Sheffield, UK, warned: “I wanted to be reassured when I heard that the Covishield vaccine was going to stop being imported from India due to the pandemic situation this country is going through. If necessary there would be no problem with the second dose being the Oxford-AstraZeneca vaccine. This is because the two vaccines are identical, just that the Oxford-AstraZeneca vaccine made and packaged in India is known as Covishield.“.

“In the near future, most likely, the vaccines will be combined. They will be combined because all the vaccines are directed against the same viral antigen, the S-glycoprotein, from the coronavirus peak. Just like when we were kids and gave ourselves the tetanus or measles vaccine, it didn’t matter which lab made the first vaccine, the first dose, ”he said.

According to Cohen, “Likewise, it will surely be and it is already being tested that we can administer to ourselves any type of vaccine for the second dose, regardless of the first dose.. In fact, in France it has been suspended, the Oxford-AstraZeneca vaccine is no longer accepted, the government has stopped with this vaccine, those who received the first dose of Oxford-AstraZeneca will receive the Pfizer vaccine as a second dose“.

In February, researchers from Oxford University began a trial in which volunteers received a dose of Pfizer-BioNTech vaccine followed by a dose of AstraZeneca or vice versa. This month, researchers will start testing the blood of these people to see how well this method works.

Mixing vaccines can not only help avoid supply bottlenecks. Some scientists suspect that two different vaccines may work better than two doses of the same vaccine. “I think we are on the verge of getting some interesting data,” he said in dialogue with The New York Times Adam Wheatley, an immunologist from University of Melbourne in Australia.

The concept of combining vaccines – sometimes called heterologous primary stimulus– is nothing new in this era of pandemic. For decades Scientists have studied this strategy in hopes of finding highly effective combinations against a variety of viruses. like influenza, HIV and Ebola.

However, scientists haven’t gotten much results from all of this research. It was very easy to show that two vaccines could work well together in one mouse. But it is very difficult to conduct real clinical trials with a combination of vaccines. “For a single company to develop two parallel arms of a vaccine, it takes twice as much work and twice as much,” he said. Wheatley.

For decades, scientists have studied this strategy in hopes of finding highly effective combinations against a variety of viruses, including influenza, HIV, and Ebola.

“Interchangeability between vaccines is and has been an area of ​​interest in vaccinology over time. because it makes it very easy from an operational point of view; promotes adherence to immunization programs and avoids missed opportunities. However, a characteristic of these vaccines is that at this time it is advisable not to exchange them. Therefore, although this is a more than interesting initiative, it would be important to verify that they can be interchangeable. From the hypothetical it seems plausible ”, explained consulted by this means, the doctor Francisco Nacinovich, head of infectology of the Cardiovascular Institute of Buenos Aires and member of the vaccines commission of the Argentine Society of Infectology.

Wheatley and his colleagues have tested vaccines using proteins in mice. In a first dose, they injected all of the spike protein into the animals. For the second dose, they injected only the peak of the peak, a region known as the receptor binding domain (RBD). So was it they discovered that the combination worked better than two doses of the peak or the RBD.

The scientists suspect that the first dose produces a wide range of antibodies which may stick to parts of the spike protein extension and that the second dose leaves a large amount of antibodies particularly powerful at the tip of the peak. This mixture of antibodies does a better job together in fighting the coronavirus. “We can practically take the initial immunity that came from this cutting edge vaccine and then really focus on this RBD,” the expert said.

According to specialists recently consulted by Infobae, there is no guarantee that the benefits of the vaccine combination will be found in clinical trials. In this sense, the pediatric infectious doctor Eduardo Lopez (MN 37586) pointed out that “There are currently no published studies on so-called vaccine interchangeability.” “Nothing is confirmed, But it’s an interesting line which deals with the possibility of exchanging vaccines; if the results are given in the expected direction, the logistical aspects can be greatly improved ”, estimated the expert, for whom“ there is still time to confirm it ”.

The infectious disease doctor agreed with him Roberto Debbag (MN 60253), who is of the opinion that “This is what is coming, the likelihood of combinations between formulations ”, but admitted that“ until the data is published, exchanges of different vaccine manufacturing platforms cannot be carried out.

“Those that can be traded are those of the same group, for example those composed of adenoviruses, whether they are chimpanzees or humans ”, he developed. Lopez, and in this sense, he gave an example: “A first dose of adenovirus 26 could be administered with the Johnson and the second with adenovirus 5 of Sputnik V ”.

Bernard Moss, virologist National Institute of Allergies and Infectious Diseases, He suspects that several companies will be willing to allow their vaccines to be tested in combination. “It is always positive to be a part of something that will be used,” he said, “than to be the sole owner of something that will not be used.”

Even like that, Naor Bar-Zeev, vaccine expert Johns Hopkins University, pointed out that “In the absence of studies, vaccine doses should not be mixed.” “If people accidentally get a vaccine different from the second dose than the first, it will probably work well and be well tolerated, but evidence is needed to be sure,” he concluded.

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