Characterization of Human Antibody Responses to Dengue Virus Infections in a Sri Lankan Pediatric Cohort Public Deposited

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  • March 19, 2019
Creator
  • Corbett, Kizzmekia
    • Affiliation: School of Medicine, Department of Microbiology and Immunology
Abstract
  • Dengue virus (DENV) is the most significant mosquito-borne viral infection of humans. People infected with dengue viruses present with subclinical (inapparent) or clinically-apparent infections ranging from undifferentiated fever to dengue hemorrhagic fever or dengue shock syndrome. It is not completely understood why some people get more severely ill from DENV infections than others, but antibody responses have been implicated in playing a role facilitating severe dengue disease. To that end, we analyzed samples from a pediatric dengue cohort study in Sri Lanka to explore if antibody responses differentiated clinically inapparent and apparent infections. 799 children living in a heavily urbanized area of Colombo, Sri Lanka were followed for one year; samples were collected at enrollment, at follow-up, and intermittently from any child who acquired fever. Using those samples, we first obtained accurate estimates of the incidence of DENV infection and disease in the cohort. At enrollment, dengue sero-prevalence was 53.07% demonstrating high transmission in this population. Over the study year the incidence of DENV infection and disease were 8.39 (95% CI: 6.56-10.53) and 3.38 (95% CI: 2.24-4.88), respectively per 100 children per year. All together, we identified 35 primary (20 inapparent and 15 apparent) and 32 secondary/repeat infections (20 inapparent and 12 apparent) over the 12-month study period. The ratio of inapparent to apparent infections was 1.48:1. Secondly, we defined temporal regulation of the DENV-infected children's antibody responses. Children who experienced primary infections had broad, serotype cross-neutralizing responses that narrowed in breadth to a single serotype over a 12-month period post infection. In children who experienced repeat infections, IgG antibody levels fluctuated following infection, but neutralization breadth remained steady. Thirdly, we observed baseline antibody responses of children who got repeat infections. Children with pre-existing monotypic neutralizing responses were more likely to develop fever than children with cross-neutralizing responses. Pre-existing DENV neutralizing antibodies were correlated with protection from apparent dengue disease. Our results will be useful for obtaining more accurate estimates of the burden of dengue in the Indian subcontinent, and, most importantly, provide insight on protective antibody responses as they may be important for vaccine development.
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  • In Copyright
Advisor
  • Heise, Mark
  • De Silva, Aravinda Manu
  • Swanstrom, Ronald
  • Baric, Ralph S.
  • Webster-Cyriaque, Jennifer
Degree
  • Doctor of Philosophy
Degree granting institution
  • University of North Carolina at Chapel Hill Graduate School
Graduation year
  • 2014
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  • Chapel Hill, NC
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