Covid vaccines adapted to variants are still promising

When the omicron variant appeared, laboratories and researchers began a new vaccine race: to produce an updated immunizer to prevent vaccine escape by the new strain.

In addition to avoiding explosions of Covid cases, the improvement of the compositions is considered strategic by specialists because, the more the virus circulates, the greater the chance that it will develop variants that can escape the protection provided by vaccines.

However, these innovations remain something for the future, as pharmaceutical companies are still conducting studies for the development of this new generation of vaccines.

Updating immunizers based on mutations in the viruses or the development of vaccines that manage to maintain a high level of efficacy even with these variations is already common for vaccines against other diseases, recalls Flávio Fonseca, president of SBV (Brazilian Society of Virology). and virologist at the microbiology department at UFMG (Federal University of Minas Gerais).

“We know that an intrinsic characteristic of some viruses is that they mutate more frequently than others,” says Fonseca. One of these cases is the influenza virus which, because of its high mutation rate, has its vaccines renewed every year.

With Sars-CoV-2 it is no different, as numerous variants have been recorded throughout the pandemic. However, it is still considered a new virus, making it difficult to develop an epidemiological surveillance network that systematically works on mutations — something that already happens with influenza.

“As we are still living in a Covid-19 pandemic situation, we do not have well-established standards, making it difficult to set up a surveillance system. this surveillance system more effective”, says the virologist.

Even with this instability, some pharmaceutical companies have already paid attention to the main variants, such as the ômicron, in order to update their vaccines.

Pfizer, for example, stated that “once the existence of a new variant is confirmed […] studies on the impact of the new strain on the effectiveness of the vaccine currently distributed are starting and, based on the information from these studies, they assess the need to develop a new version of the immunizer”.

According to the pharmaceutical company, a study is being carried out for a specific vaccine against the micron with results expected for the first half of this year.

A similar initiative is carried out by Moderna, whose vaccine is not yet available in Brazil. At a March 24 conference, the company disclosed the different vaccines it has been working on. For omicron, for example, phase two studies are being carried out, lacking phase three to assess the effectiveness of the immunizer.

The Butantan Institute, responsible for Coronavac in Brazil, said that together with Sinovac – the Chinese manufacturer of the vaccine – it is already working on an update “not only for Ômicron, but also for variants in general”.

Janssen, on the other hand, said it is constantly evaluating the vaccine’s effectiveness against new variants, but indicated that there is a “growing body of evidence that shows that the vaccine’s effectiveness […] remains strong and stable over time, including against circulating variants such as omicron and delta”.

Similarly, AstraZeneca said it is not working on updates to its vaccine or on the development of a new one, as “so far there is no scientific evidence on the need to modify existing vaccines”.

The dilemma is that developing a new vaccine for the variants can occur while other strains, with the potential to become prevalent, emerge.

“It doesn’t do much good to make a vaccine today for the Ômicron and six months from now, when it is produced and distributed, there will already be another variant that is in circulation, and the immunizing agent is not very effective”, says Renato Kfouri, director of Sbim ( Brazilian Society of Immunizations).

One way to circumvent this problem would be research into so-called universal vaccines, which retain immunization capabilities even with variants.

In Brazil, such initiatives are already being developed. One of these examples is at UFMG, with the collaboration of Batista. He explains that much of the research uses the S protein (spike) —used by the virus to penetrate the human cell— for the development of vaccines.

The problem is that it is much more common for this protein to undergo mutations, causing the immunizer to lose some effectiveness depending on the variant.

“An alternative would be to use other proteins of the virus and not just the S protein. For example, there is the N protein (nucleocapsid), which is not exposed on the surface of the virus, so it is less susceptible to mutations”, he says.

At UFMG, the researchers developed a chimera, the name given to an artificial protein. In it, the N and also the S protein are found because, even with its high susceptibility to alteration, it remains important for the development of the immune response.

Currently, the immunizer is in the animal studies phase and hopes to obtain authorization from Anvisa (National Health Surveillance Agency) to be able to proceed to human trials.

Another Brazilian project is for a nasal vaccine that is being developed in the laboratory of Incor (Instituto do Coração) at Hospital das Clínicas at USP.

“A vaccine that induces a good response in the upper airways is important, because it would stop the infection and, potentially, the transmission of the virus”, says Jorge Kalil, the researcher responsible for this other vaccine candidate.

He explains that, in this project, the idea is that the vaccine induces an antibody called secretory IgA, commonly found in mucous membranes. “This would protect the population against an infection. In addition, we also have components to induce a good cellular response that would be advantageous in fighting the infection, if it occurs.”

This other type of T cell-based response has already been investigated, as it has been shown to be important against Sars-CoV-2 infections. This path would also be useful, as it has the chance to confer an immune response even with variations that the virus suffers in the S protein.

At the moment, Kalil plans to carry out the clinical phases in humans, but finds “difficulties in producing the batches that are applicable in the clinic to start the tests”.