Abstract
Although heterotypic secondary infection with dengue virus (DENV) is associated with severe disease, the majority of secondary infections are mild or asymptomatic. The mechanisms of antibody-mediated protection are poorly understood. In 2010, 108 DENV3-positive cases were enrolled in a pediatric hospital-based study in Managua, Nicaragua, with 61 primary and 47 secondary infections. We analyzed DENV-specific neutralization titers (NT50), IgM and IgG avidity, and antibody titer in serum samples collected during acute and convalescent phases and 3, 6, and 18 months post-infection. NT50 titers peaked at convalescence and decreased thereafter. IgG avidity to DENV3 significantly increased between convalescent and 3-month time-points in primary DENV infections and between the acute and convalescent phase in secondary DENV infections. While avidity to DENV2, a likely previous infecting serotype, was initially higher than avidity to DENV3 in secondary DENV infections, the opposite relation was observed 3–18 months post-infection. We found significant correlations between IgM avidity and NT50 in acute primary cases and between IgG avidity and NT50 in secondary DENV infections. In summary, our findings indicate that IgM antibodies likely play a role in early control of DENV infections. IgG serum avidity to DENV, analyzed for the first time in longitudinal samples, switches from targeting mainly cross-reactive serotype(s) to the current infecting serotype over time. Finally, serum avidity correlates with neutralization capacity.
Highlights
The four serotypes of the flavivirus dengue virus (DENV1–4) cause the most common mosquito-borne viral disease in humans worldwide, with 50–100 million people infected annually and over 3 billion people at risk [1]
The disease can be more severe and sometimes fatal, with signs of bleeding and vascular leakage leading to shock (Dengue Hemorrhagic Fever/Dengue Shock Syndrome)
DENV-specific serum neutralizing capacity may play a role in protection
Summary
The four serotypes of the flavivirus dengue virus (DENV1–4) cause the most common mosquito-borne viral disease in humans worldwide, with 50–100 million people infected annually and over 3 billion people at risk [1]. DENV infection can be asymptomatic or cause a spectrum of disease ranging from classical dengue fever (DF) to more severe, life-threatening forms termed dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS) [2]. Short-lived PCs are active during acute infection, while long-lived PCs (LLPCs) migrate to the bone marrow and are responsible for long-term humoral immunity [6,7]. MBCs, which retain antigen-specific Abs at their surface, and LLPCs, which secrete antigen-specific Abs, undergo affinity maturation, and only clones bearing Abs with the highest affinity survive long-term [8]. This process takes several weeks after acute infection and continues despite the absence of circulating antigen. The vast majority of 2u DENV infections are asymptomatic or only result in mild disease [16], suggesting a protective immune response [17]
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