Singapore - Immunology: For one and for all

The infection of one dengue virus subtype can lead to the production of antibodies that confer protection against other dengue virus subtypes

Dengue fever is a mosquito-borne illness caused by the dengue virus that is endemic in Singapore and other tropical regions of the world. Over half of Singaporeans harbor antibodies that confer protection against the dengue virus, but how soon after infection these antibodies are produced in the body, and how broadly protective they are against the different strains, or subtypes, of the dengue virus, is unclear. An international team of researchers led by Katja Fink at the A*STAR Singapore Immunology Network1 have now observed an unexpectedly early and high production of antibodies in the human body after both primary and secondary infection of the dengue virus.

Dengue virus infection can cause a variety of symptoms, ranging from fever, pain, rash to hemorrhage — even death. Severe symptoms are seen more frequently in patients who have been infected with dengue virus more than once. These so-called secondary infections are therefore more dangerous than primary infections.

Fink and co-workers took blood samples from individuals who were presented to the clinic with fever and screened the samples for dengue viruses, as well as antibodies against dengue viruses. Based on the test results, they classified the patients into one of three groups: normal (non-dengue) fever, primary dengue infection, and secondary dengue infection.

The researchers found that blood samples from patients with dengue infection contained a much higher number of antibody-producing immune cells than in those from patients with normal fever. When they exposed cells in culture to antibodies produced by these immune cells, they found the cells were protected against not just one but four major dengue virus subtypes. Antibodies from patients with secondary infection seemed to neutralize infection by all four dengue strains even better than those from patients with primary infection, suggesting that their immune response to re-exposure to the virus is stronger than the response of patients who are exposed to the virus for the first time.

"Our findings can explain why dengue patients are protected against all four dengue strains for several weeks after infection with one strain,” says Fink. “However, the enormous numbers of activated cells also create inflammation in the body, which can contribute to the symptoms observed in dengue patients." As patients with secondary infections have stronger, more improperly regulated immune responses than those with primary infections, the findings could explain why secondary infection is often more severe than primary infection.

The A*STAR-affiliated researchers contributing to this research are from the Singapore Immunology Network and theGenome Institute of Singapore

References

1. Balakrishnan, T. et al. Dengue virus activates polyreactive, natural IgG B cells after primary and secondary infection. PLoS One 6, e29430 (2011). | article