Dynamics of dengue antibodies: Transplacental transfer, decline after birth and the serotype specific response to infection among infants and children in Thailand

Introduction. Dengue is an emerging vector borne disease with four serotypes that cause between 500 000 and a million cases of disease every year. Dengue control is challenged by a lack of knowledge on circulation of the virus in the population and the absence of a vaccine. Dengue vaccines are in an advance state of development but vaccination of infants is challenged by circulating maternal dengue antibodies.;Methods. A collaboration was established with Sanofi Pasteur in France and the Armed Forces Research Institute for Medical Sciences in Bangkok and data on antibody levels in mothers, infants and schoolchildren from their respective cohort studies was analyzed. The decline of maternal dengue antibodies was explored using longitudinal data analysis with separate models for the mean and covariance structures. Patterns in the serotype specific antibody response to infection were measured using multinomial regression methods.;Results. Transplacental transfer of neutralizing dengue antibodies is a selective process that depends on maternal antibody concentrations. Similarly, the decline rate of these antibodies is dependent on antibody levels at birth and different at different age intervals. No associations could be detected between social-economic, maternal or infant factors and antibody decline rates. Finally, patterns could be detected in the serotype specific antibody response to dengue infection that could be used to predict the infecting dengue serotype.;Conclusions. Maternal dengue antibody titers are not representative of infant antibody levels since many factors determine the proportion of neutralizing antibodies that is transferred. Projected infant antibody titers based on maternal levels have limited value in studies on dengue pathogenesis and vaccination. Different decline rates of maternal antibodies at different age intervals make projections of expected antibody levels in infants even less meaningful. Detailed studies that measure neutralizing antibody titers in infants and incidence of severe dengue are required for a better understanding of dengue pathogenesis and vaccine efficacy. Inference on circulating dengue serotypes based on serotype specific neutralizing antibody titers before and after infection could be of great use in dengue control efforts and monitoring its global spread.