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Paper of the Month March 2012

Dengue Virus Infection-Enhancing Activity in Serum Samples with Neutralizing Activity as Determined by Using FcγR-Expressing Cells

2012. PLoS Neglected Tropical Diseases 6(2): e1536.

Authors

Meng Ling Moi, Chang-Kweng Lim, Kaw Bing Chua, Tomohiko Takasaki, Ichiro Kurane

Abstract

Dengue has become a major international public health concern in recent decades. There are four dengue virus serotypes. Recovery from infection with one serotype confers life-long protection to the homologous serotype but only partial protection to subsequent infection with other serotypes. Secondary infection with a serotype different from that in primary infection increases the risk of development of severe complications. Antibodies may play two competing roles during infection: virus neutralization that leads to protection and recovery, or infection- enhancement that may cause severe complications. Progress in vaccine development has been hampered by limited understanding on protective immunity against dengue virus infection. We report the neutralization activity and infection-enhancement activity in individuals with dengue in Malaysia. We show that infection-enhancement activity is present when neutralizing activity is absent or low, and cross-reactive neutralizing activity may be hampered by infection-enhancing activity. Conventional assays for titration of neutralizing antibody do not consider infection- enhancement activity. We used an alternative assay that determines the sum of neutralizing and infection-enhancement activity in sera from dengue patients. In addition to providing insights into antibody responses during infection, the alternative assay provides a new platform for the study of immune responses to vaccine.