Faced with the worst dengue epidemic in recent decades, Brazil has decided to do so first country in the world to use the new Japanese vaccine Qdenga. A development that… Also draws attention to efforts by Cuban scientists to develop a dengue vaccine.
The World Health Organization (WHO) has pointed out that the number of reported dengue cases has increased tenfold in recent decades, rising to over 5 million per year. This reflects a global challenge as the disease spreads to areas where it was not previously widespread, including Europe and the United States.
Although Cuba is not one of the countries reporting the most dengue cases, the disease is still a recurring problem on the island. Back in the 1980s, a dengue epidemic had a serious impact on the Cuban population, resulting in thousands of cases and tragic deaths.
Since 1992, Cuban scientists have been working on developing a dengue vaccine. The research began with promising results, including the identification of a protein called Domain III that could trigger immunity to dengue fever in primates. Various approaches have been taken over the years to develop an effective vaccine candidate, including a candidate called TetraDIIIC, which achieved promising results in preclinical studies and pursued the concept of a quadrivalent vaccine candidate that can protect against all four serotypes of the dengue virus – one of the key goals for any vaccine to be effective against the disease, and something the Takeda lab has already achieved.
Recent developments indicate that Cuba’s research on the vaccine candidate TetraDIIIC has now been discontinued and that researchers on the Caribbean island are pursuing a new strategy. The number of publications with the keyword “Cuba dengue vaccine” on the Pubmed website has fallen dramatically since 2019, after dozens of scientific articles had appeared on this topic in previous years. In addition, no more publications on the TetraDIIIC domain have been reported to Pubmed since this year.
This may have to do with the safety profile of the Cuban vaccine candidate and the development of Dengvaxia related, the first approved dengue vaccine in the world.
Dengvaxia is a vaccine developed by a French pharmaceutical company based in the United States, Sanofi Pasteur. After more than 733,000 minors were vaccinated in the Philippines in 2017, the administration of the drug was banned in that country after the deaths of children with severe forms of the disease were noted.
Everything seems to indicate that this is due to a phenomenon known as antibody-dependent enhancement (ADA), which is characteristic of dengue. When a person becomes infected with a virus from one of the four dengue serotypes, the infection is usually asymptomatic or very mild. However, if a person becomes infected with a virus of one of the other serotypes in the future, there is a chance that instead of a banal infection, a severe form of the disease will occur, which can lead to death.
In addition to the number of Cuban Pubmed publications, there is further evidence that Cuban scientists have reconsidered their strategy and are pursuing a new approach.
So reported the national media iIn September 2022 briefly about the presentation by Dr. S. Gerardo Guillén Nieto – member of the research team responsible for the development of the vaccine since the first published works and director of biomedical research at the Center for Genetic Engineering and Biotechnology in Havana (Centro de Ingeniería Genetica y Biotecnología – CIGB) on “the Cuban strategy for the dengue vaccine” before the highest authorities of the country.
In March 2023, the CIGB announced the social media said that the Cuban strategy to obtain a vaccine against this disease was based on recombinant proteins, but on this occasion it referred to the use of structures other than those pursued with TetraDIIIC. According to the institute’s publication, it is “a very safe technological platform. We have a tetravalent candidate based on the proteins of the four dengue viruses that we are currently evaluating.”
One month later announced CIGBthat the vaccine candidate against dengue is currently in the “research development phase”. According to the publication, researchers are “beginning with preclinical studies in which they will test two different formulations to determine which one will enter the clinical trials,” that is, which one will be tested in humans.
On the same day, the CIGB’s research director stated in a Interview with the Spanish news agency EFE that the Cuban researchers are “experimenting with the non-structural proteins” “instead of the protein found in the virus membrane.”
“Cuba is trying to produce the vaccine in a different way” and, according to the EFE article, “it is the only country that is trying to do it in this way” and is experimenting with non-structural proteins which are not part of the envelope of the viruses, but are encoded by their genes.
According to Guillén Nieto, the aim is to develop a vaccine that enhances the recipient’s cell-mediated response and not that of his antibodies.
This would avoid ADA, or immunoamplification, as the phenomenon is also called, and generate an important cellular response that would prevent severe forms of dengue.
As already noted, there are only two approved vaccines in the world: Dengvaxia, manufactured by a French laboratory whose safety problems have severely hampered its distribution, and Qdenga, also known as the Japanese vaccine, whose cost per dose is $52, according to an Argentine newspaper. Qdenga producers are unable to meet the demand of a country like Brazil, let alone the demand of almost half of the world’s population exposed to the virus.
The strategy of having a national preparation produced in Cuba would therefore be extraordinary in many respects. On the one hand, the country would significantly reduce the costs of immunizing its population. Secondly, it would open up a market of billions of people in the world exposed to dengue fever throughout the tropical and subtropical belt, which would bring obvious economic benefits.
However, the Cuban team’s research faces challenges, including regulatory hurdles and the need for further clinical trials. Developing a vaccine requires time and resources, but the potential benefits for Cuba and the global community are enormous.