Deciphering antibody-dependent enhancement, surprising discovery from dengue vaccine

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ADE, the full name of Antibody-dependent Enhancement, that is, antibody-dependent effect, has always been an important juncture in vaccine development.

The ADE effect, which is closely related to the effect of bad antibodies, was first observed by virologists in Australia in 1964. At that time, scientists put the virus in a low concentration of immune serum - as to why it is a low concentration, the reason is that the concentration of antibodies in the low concentration serum is very low, when the virus is in a very low concentration of antibodies. In the environment, it is easier to observe.

Scientists have observed that in the low concentration of antibody serum, the replication of the virus will not be inhibited, but will be promoted, which makes it easier for the virus to infect other normal cells of the human body. Since then, this effect Scientists named it the ADE effect.

In 1977, scientists studying dengue fever linked the effect of ADE with the clinical manifestations of severe dengue fever caused by dengue fever, which means that a clear virus with ADE phenomenon, dengue virus, has been reported in history.

Specifically, the WHO began to arrange for the development of dengue vaccines in 1978. Technologies such as live attenuated vaccines, recombinant subunit vaccines, and inactivated vaccines have been developed.

On December 9, 2015, Sanofi Pasteur announced that Dengvaxia, a dengue vaccine developed by the company, was approved by the Mexican Federal Committee for the Prevention of Health Risks (COFEPRIS) for the prevention of dengue fever in people aged 9-45 years old living in dengue-endemic areas. The disease caused by four serotypes of dengue virus has become the first dengue vaccine product approved in the world.

So far, how long has this dengue vaccine been developed? From 1978 to 2015, it has experienced 37 years of research and development. It's just, is the vaccine developed in 37 years safe?

In April 2016, the Philippine Department of Health decided to vaccinate primary school students in the Philippines against dengue fever. One year later, on December 5, 2017, the Philippine government stopped the vaccine due to the death of many children suffering from dengue fever and complications after being vaccinated. The reason is the so-called ADE effect.

First of all, the dengue virus is similar to COVID-19, and it is also of many strains, and it is also inoculated in several injections. So, what about the dengue vaccine in the Philippines? Dengvaxia is a live attenuated dengue vaccine produced by Pasteur, which includes the genes of four types of dengue virus, that is, four dengue virus strains. The vaccine is divided into three separate injections, administered 6 months apart.

In theory, Denvaxia should be effective against all four types of dengue, but in practice it is not. It is safe to vaccinate children who have already had one of the dengue diseases, while vaccinating children who have not been exposed to dengue may increase the risk of disease .

Safety advocates in the Philippines have called it "the largest government-funded clinical trial and public health hoax in the history of the Department of Health, which has harmed 830,000 children and their families." Since the Denvasia vaccine controversy, Filipino parents' confidence in the vaccine has dropped from 82% in 2015 to 21% in 2018; meanwhile, the number of parents who believe the vaccine is important has dropped from 93% to 32%.

By November 2017, Pasteur announced on its website that "the vaccine has been found to increase the risk of hospitalization and cytoplasmic leak syndrome in children (regardless of age) who have not been exposed to dengue; People infected with dengue are not vaccinated." Pasteur announced that new testing data showed that the Denvaxia vaccine can cause serious complications in people who are seronegative (that is, in people who have not previously been infected with any type of dengue virus).

This is a vaccine for dengue fever. After 37 years of development, a vaccine that will cause ADE effects will be vaccinated. If it is not vaccinated, there will be no problem, but if it is vaccinated, it will cause more serious problems.