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Cuba’s quest to develop a dengue vaccine using non-structural proteins

Achieving a dengue vaccine is a historical desire of tropical countries where it is endemic. Cuba, which took on this challenge in 1992, now has two formulations in the preclinical study phase.

This step might seem like a small thing, but it is not. This is how Gerardo Guillén, director of Biomedical Research at the Center for Genetic Engineering and Biotechnology (CIGB) explains it in an interview with EFE.

It means a leap that brings the country closer to achieving a shield against a disease that kills 2.5% of those hospitalized with a serious condition, according to figures from the World Health Organization (WHO).

Guillén clarifies that dengue is not just any virus and coming up with an effective formula is a complex challenge. In the first place, he comments, it is a virus that travels through the mosquito (Aedes aegypti), a cross that countries like Cuba carry.

But what really makes this pathogen a headache for laboratories – and a danger to people – are its four serotypes.

Getting sick with one of the four can become a sentence, since the next contagion means developing stronger symptoms than the first.

“When you are infected with a serotype, you are protected for life from that serotype. But not against the others. With the others, the opposite happens: you become sensitized,” he says from the CIGB headquarters in Havana, the center that managed to develop the Abdala vaccine. , the first Latin American against covid-19.

Many times, adds the scientist, that first infection goes unnoticed. But it is in that second mosquito bite where the real threat is hidden.

“This is known as immunoamplification. Your system recognizes the second virus but does not neutralize it. What it does is bind (to it) and take it to the cells, where it will multiply,” he adds.

Guillén emphasizes that this very particular nature of dengue causes the risk that the cure is worse than the disease.

“The same thing that a natural disease does (that a first contagion makes the second much more harmful) can happen with the vaccine (…) (in that case) it is better not to have been vaccinated,” he explains.

In other words, the inoculation would only work if the vaccinated person had already suffered from the disease before.

There is already a precedent. In 2017, the Philippines stopped administering the Dengvaxia vaccine, from the French Sanofi Pasteur, after registering the deaths of minors with serious cases.

However, there are also successful cases. In March, Brazil approved the registration of the tetravalent drug from the Japanese pharmaceutical company Takeda, with 80% effectiveness and with the approval of the European Medicines Agency (EMA).

THE CUBAN FORMULA

As Guillén explains, Cuba seeks to make the vaccine in another way. And, he adds, it is the only country that is trying it in that way.

Instead of using the protein found in the virus’s membrane, the island scientists experiment with its non-structural proteins (which encode the virus’s genes).

The scientist explains that what they are looking for is for the vaccine to strengthen the cellular response of the person who receives it and not that of their antibodies. In this way, according to what they hope will be verified in the laboratory, this “immunoamplification” could be avoided, which makes the dengue vaccine so difficult.

“The objective is that this cellular response is sufficient to protect (from the four serotypes). We are going to have a guarantee of safety, but it remains to be shown whether we are going to have sufficient efficacy to protect against the disease,” he concludes.

Currently, the Cubans are testing two different formulations on monkeys. What they will try to decipher is which will be the “finalist” that will go to a next stage months later.

The director of Biomedical Research at the CIGB clarifies that the vaccine -even if nothing fails- will not arrive this year. He stresses that it’s more important to be late but get it right than to work to a schedule.

He added that the processes would be faster without the obstacles posed by the US sanctions against the island, which make it difficult to do things as simple as getting equipment or making bank transfers to intermediaries to purchase supplies.

IN CUBA, NO CONTAGE DATA

The development of the Cuban vaccine against dengue is currently the number one priority for island science, Guillén acknowledges. This is largely due to the current situation in the country.

“In recent months we have had the circulation of the four viruses in Cuba. (Therefore) there is more awareness (that is, more risk of a second infection) and more extensive epidemics are expected to occur,” he summarizes.

There are no public data on the total number of infections during 2022, nor on deaths from dengue. However, the independent press echoed the significant increase in infections.

Cuba notified 3,036 cases in the first half of last year. But then it registered 11,634 reactive cases of dengue in the second week of August alone.

According to the authorities, in 2022 the country broke the record for the number of breeding sites for the Aedes aegypti mosquito in 15 years for the second year.

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