Although there is a vaccine against dengue fever, it is often ineffective against the pathogen, which is made up of four different viral serotypes. But the recent discovery of a subpopulation of antibodies in vaccinated children should make it possible to design a more effective vaccine.
- Currently, there is only one licensed dengue vaccine, Dengvaxia, but it is only partially effective.
- The reason: dengue fever is caused by 4 different serotypes, and the vaccine stimulates the production of neutralizing antibodies which recognized a part of the virus (the epitope) unique to each serotype.
- In the event of reinfection with another serotype, the antibodies from the first infection help the virus to replicate, which can cause a serious immune reaction.
Also called “tropical flu”, dengue fever is a tropical hemorrhagic fever linked to an arbovirus, transmitted by the female tiger mosquito. According to the World Health Organization (WHO), 390 million cases are recorded each year in the world, including 500,000 of “haemorrhagic” dengue fever, that is to say which are fatal in more than 2.5% cases.
To date, there is only one approved vaccine against dengue fever: Dengvaxia, developed by Sanofi Pasteur. Authorized in the countries of the European Union since the end of 2018, it is reserved for people aged 9 to 45 who have been infected with the dengue virus in the past and who live in regions where this infection is endemic. The occurrence of a previous infection with a dengue virus must then be proven by a positive test result. The vaccine is then given in three doses at an interval of six months.
If there is still only one viable dengue virus vaccine today, it is because the pathogen that causes this disease is actually made up of four different types of virus, or serotypes.
But a discovery made by researchers at the University of North Carolina (USA) could lead to the development of effective vaccines against dengue fever. Their findings have just been published in the Journal of Clinical Investigation.
A vaccine that can cause a severe immune reaction
All four dengue virus serotypes are mosquito-borne flaviviruses that infect hundreds of millions of people each year in Southeast Asia, the Western Pacific islands, Africa and Latin America. Although rarely fatal, the virus can cause serious illness, especially when a person who has been infected with one serotype (and recovers) is subsequently infected with a second serotype.
This is because of the immune response: antibodies from the first infection help the virus replicate in the second infection through a process called antibody-dependent enhancement. A dengue vaccine-induced antibody response weighted against a single dengue virus serotype can mimic this phenomenon. The vaccine may therefore prove to be more dangerous than protective.
A vaccine that must specifically target the 4 dengue serotypes
Currently, several dengue vaccines are in development, and most show that they induce neutralizing antibodies against all four serotypes. However, research has also shown that the creation of neutralizing antibodies alone is not synonymous with protection against clinical disease.
In this new study, researchers compared the properties of antibodies against wild-type dengue viruses and the properties of antibodies produced by Dengvaxia, which Sanofi Pasteur created using the four dengue virus serotypes in a single wording.
The experiments showed that wild-type infections induced neutralizing and protective antibodies that recognized a part of the virus – an epitope – unique to each serotype. The vaccine, on the other hand, primarily stimulated neutralizing antibodies that recognized epitopes common to all serotypes. In vaccine trials, these antibodies did not protect children against dengue fever. Contrary to what research previously thought, not all dengue neutralizing antibodies are therefore protective in humans.
“Our results suggest that a safe and effective dengue virus vaccine must stimulate neutralizing antibodies targeting unique sites on each of the four dengue serotypes. And not just neutralizing antibodies against cross-reacting epitopes common to all four types of dengue”summarizes Cameron Adams, co-author of the study.
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