Is it possible to combine two doses of different vaccines?

As more and more vaccines are licensed, researchers are testing combinations. Some are in clinical trials, while others are only tested on animals.

In January, United Kingdom implemented a change in its vaccine 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 this moment, there was no scientific data showing that the mixture of two coronavirus vaccines was safe and effective. But that could change soon.

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.

“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 Argentinian Society of Infectology.

Wheatley and his colleagues 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 antibody 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.

Other vaccine combinations may have advantages on their own. Some vaccines, especially those that use protein, are very good at generating antibodies. Others, like viral vectors, are better able to train immune cells. A viral vector followed by a protein load could offer the best of both worlds.

Jakob Cramer, director of clinical development at Coalition for epidemic preparedness innovations (CEPI), a vaccine development organization, noted that vaccines using viral vectors are not the only ones where the combination might work. In fact, other combinations could generate a different and more effective immune response than those of a single type of vaccine. “In terms of immunity, there are several arguments in favor of exploring the heterologous primary stimulus ”, commented To screw up.

However, specialists warn that there is no guarantee that the benefits of the vaccine combination will be found in clinical trials. Consulted on this subject by Infobae, 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 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 made up of adenoviruses, whether chimpanzees or humans, ”he added. 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 ”.

After the UK came under fire in January for suggesting the vaccines could be combined, researchers of the Oxford University they put this idea into practice in a formal test. In an essay titled Com-Le, recruited 830 volunteers to test the two vaccines approved by the British government: the AstraZeneca adenovirus and that of Pfizer-BioNTech.

The Pfizer-BioNTech vaccine uses very different technology to produce advanced proteins in the body. It contains tiny bubbles with genetic molecules called RNA. When the bubbles fuse with cells, they use RNA to make advanced proteins.

A group of volunteers lWe apply a dose of Pfizer-BioNTech followed by a dose of AstraZeneca, while another will receive them in reverse order. The other volunteers will receive the normal two-dose version of the same vaccine.

Later this month, the Oxford team will take blood samples from the volunteers, analyze their antibodies and immune cells to see if the heterologous primary stimulus generates about as strong an immune response than two doses of each of the authorized vaccines.

If more vaccines are licensed in the UK, perhaps the Com-Cov testing team will add them to its testing. “The vaccine of AstraZeneca and the Oxford University hypothetically could be combined with Sputnik V, and in fact between them they have a collaboration project signed in December “, he estimated. Lopez, in reference to the cooperation agreement to improve their vaccines against the coronavirus that both have signed.

Consulted on the messenger RNA vaccines of Moderna and Pfizer, López ruled that “they could be traded because they use the same technology, but Modern uses 100 micrograms of antigens against 25 from Pfizer, there is a problem with the composition of the doses that should be kept ”.

“But as long as there are no studies in humans, it is not possible to venture much further,” he insisted, and regarding the one-dose vaccines of Johnson , Cansino or Sputnik Light he pointed out that “there is no work that says how long the immunity lasts.

As the number of licensed vaccines increases, the possible combinations that can be used will increase. Recently, researchers from National Food and Drug Control Institutes of China expanded their research on heterologous primary activators to test four vaccines already licensed or in advanced clinical trials: These are adenovirus, protein, RNA, and coronavirus vaccines that have been inactivated with chemicals.

The first dose the researchers injected into the mice was from one vaccine and the second from another. Some of the combinations caused the animals to produce stronger immune responses than those who received the same vaccine at both doses. Whether scientists do further testing with other vaccines will depend on the willingness of the manufacturers.

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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