Maternal Antibody and Viral Factors in the Pathogenesis of Dengue Virus in Infants

Abstract

The pathogenesis of dengue in infants is poorly understood. We postulated that dengue severity in infants would be positively associated with markers of viral burden and that maternally derived, neutralizing anti-dengue antibody would have decayed before the age at which infants with dengue presented to the hospital. In 75 Vietnamese infants with primary dengue, we found significant heterogeneity in viremia and NS1 antigenemia at hospital presentation, and these factors were independent of disease grade or continuous measures of disease severity. Neutralizing antibody titers, predicted in each infant at the time of their illness, suggested that the majority of infants (65%) experienced dengue hemorrhagic fever when the maternally derived neutralizing antibody titer had declined to <1 : 20. Collectively, these data have important implications for dengue vaccine research because they suggest that viral burden may not solely explain severe dengue in infants and that neutralizing antibody is a reasonable but not absolute marker of protective immunity in infants.

Prospective birth cohort in a hyperendemic dengue area in Northeast Brazil: methods and preliminary results

“…2,17 . This maternal anti-dengue immune profile seems to be different from studies conducted in pregnant women in Asian countries where the majority of pregnant women were immune against two or more DENV serotypes 5,8,9 . In these Asian countries, unlike Brazil 2 , a high proportion of dengue cases in infants progress to severe dengue forms 3,21 .…”

“…In the first six months of life, high levels of transplacentally transferred maternal anti-DENV antibodies appear to protect infants from symptomatic dengue 4 . However, a progressive decline in these antibodies after birth may increase the risk of developing severe dengue among infants aged 6-12 months 4,5 . It has been postulated that an immunological window characterized by subneutralizing levels of transplacentally transferred maternal anti-DENV antibodies is involved in the development of severe dengue in infants 4,5,6 .…”

“…It has been postulated that an immunological window characterized by subneutralizing levels of transplacentally transferred maternal anti-DENV antibodies is involved in the development of severe dengue in infants 4,5,6 . This has been confirmed by studies conducted in Southeast Asia, where severe dengue in children in the first months of life often occurs in primary dengue virus infection 3,5,7 .…”

Serologic Imprint of Dengue Virus in Urban Haiti: Characterization of Humoral Immunity to Dengue in Infants and Young Children

“…A special emphasis is placed on the prevention of mother-to-child transmission of HIV, and children born to HIV-infected mothers are carefully followed postpartum for evidence of HIV infection. 19 Participants and study design. The age range of the children was 7-36 months (mean age = 18.6 months, median age = 16.9 months, and intraquartile age range = 11.9-24.3 months).…”

Leukocyte immunoglobulin-like receptor B1 is critical for antibody-dependent dengue

“…Furthermore, the risk of severe disease is augmented by cross-reactive or subneutralizing levels of antibody (2,3), which opsonize dengue virus (DENV) to ligate Fc-gamma receptor (FcγR) for entry into monocytes, macrophages, and dendritic cells, a phenomenon known as antibody-dependent enhancement (ADE) of DENV infection (4,5). The resultant greater viral burden leads to increased systemic inflammation that precipitates plasma leakage, a hallmark of dengue hemorrhagic fever (6).…”