Kinetics of NS1 and anti-NS1 IgG following dengue infection reveals likely early formation of immune complexes in secondary infected patients

Dengue virus (DENV) is a major health concern throughout the world infecting up to 390 million people globally each year. Infection with any one of the four DENV serotypes produces a spectrum of clinical illness ranging from a mild undifferentiated febrile disease through to severe dengue involving fever and haemorrhage. There is currently no antiviral treatment for dengue and only one licensed vaccine with limited distribution. This study characterises the kinetics of the serological dengue biomarker, NS1, and the appearance of anti-NS1 IgG, anti-E IgM and anti-E IgG responses in patients with primary and secondary infections. Blood samples were collected daily from a cohort of 52 Vietnamese patients during the acute phase of disease. NS1 was detected in 85% of patient samples from disease onset with detection decreasing throughout the acute phase of disease. Anti-NS1 IgG detected from the fourth day of illness and anti-E IgM and IgG from the third day of illness, were all observed to increase throughout the course of the disease. During secondary infection, NS1 levels rapidly decrease with the increasing levels of anti-NS1 IgG, suggesting the possibility of NS1 immune complex formation and a potential role in the pathogenesis of the severe forms of disease associated with secondary infections.