By: Charles Ebikeme

Albert B Sabin is probably best known for his work and research on the polio virus. During World War II he worked on

and developed vaccines for encephalitis (sleeping sickness), sand-fly fever and dengue fever as well. It is his work into dengue fever during this time that is now having possible implications for vaccine development today — 60 years later.

Symptomatic dengue infection is characterized by fever, joint and muscle pain, headache, rash, vascular leakage and occasionally hemorrhage. Dengue hemorrhagic fever and dengue shock syndrome are more serious complications that result from multiple infections with the dengue virus. Severe disease in secondary infections is also a common trait of dengue.

Research into dengue fever during World War II in human volunteers showed that some level of protection from the disease is provided once a person has been infected. However, protection is strain-specific (there are 4 strains, or serotypes, of dengue virus). If in their lifetime, an individual is infected with two different strains of dengue virus, the resulting disease-immune system interaction could be deadly. This interplay of disease and immune system could mean the difference between getting a mild fever and going into a fatal circulatory failure from dengue hemorrhagic fever or dengue shock syndrome.

The findings from two independent studies in Managua, Nicaragua by researchers publishing in Science Translational Medicine now point to the mechanism of such protection.

After infection with one dengue strain, the immune system reacts normally by creating antibodies to fight the viral invaders. It is what happens during the second infection with one of the other three strains that lead the researchers to investigate further. Upon the secondary infection, those viral invader-fighting antibodies often get confused when confronted with an unfamiliar strain of dengue. The antibodies don’t fully recognize the second infection, and not only that, they seem to help the virus invade the immune system.

This sort of negative correlation of prior immunity and disease has been observed with HIV and influenza. It is only dengue that results in a severe clinical outcome.

With the development of the first ever dengue vaccine underway, “Our findings have implications for vaccine development and implementation, as the precise genetics of vaccine strains, as well as the timing and serotype sequence of infection prior to and after vaccination, play an important role in determining the outcome of infection,” said the study’s lead author Molly OhAinle in a press release.

Charles Ebikeme is a writer and scientist with a research background in tropical diseases. Possessing a MSc from the London School of Hygiene & Tropical Medicine, and a PhD in Parasitology from the University of Glasgow, Charles currently blogs and writes for the All Results Journals – a new publication system focusing on negative results – covering topics on the hidden side of the scientific publication process.

For more information about dengue and the work being done to produce and distribute a dengue vaccine, visit the Dengue Vaccine Initiative (DVI) website.