A relevant in vitro human model for the study of Zika virus antibody-dependent enhancement.

Zika virus (ZIKV) is a mosquito-borne flavivirus that has recently been responsible for a serious outbreak of disease in South and Central America. Infection with ZIKV has been associated with severe neurological symptoms and the development of microcephaly in unborn fetuses. Many of the regions involved in the current outbreak are known to be endemic for another flavivirus, dengue virus (DENV), which indicates that a large percentage of the population may have pre-existing DENV immunity. Thus, it is vital to investigate what impact pre-existing DENV immunity has on ZIKV infection. Here, we use primary human myeloid cells as a model for ZIKV enhancement in the presence of DENV antibodies. We show that sera containing DENV antibodies from individuals living in a DENV-endemic area are able to enhance ZIKV infection in a human macrophage-derived cell line and primary human macrophages. We also demonstrate altered pro-inflammatory cytokine production in macrophages with enhanced ZIKV infection. Our study indicates an important role for pre-existing DENV immunity on ZIKV infection in primary human immune cells and establishes a relevant in vitro model to study ZIKV antibody-dependent enhancement.

IgG1 and IgG4 antibodies against Aedes aegypti salivary proteins and risk for dengue infections.

Dengue virus (DENV) is an arbovirus responsible for a significant number of deaths in Latin America. This virus is transmitted through the bite of Aedes aegypti, the main mosquito vector, and Ae. albopictus. During blood uptake, the mosquito injects its saliva into the host to facilitate the feeding process. Mosquito saliva contains potent immunogens capable of inducing antibody production directly related to mosquito bite exposure intensity and disease risk. In this study, we first determined the DENV infection status by two different DENV non-structural protein 1 (NS1) based rapid tests and qRT-PCR, then measured the levels of IgG1 and IgG4 antibodies against salivary proteins of Ae. aegypti female mosquitoes in volunteers living in a dengue endemic area. Our results show that people with a positive DENV diagnosis present higher levels of IgG4 antibodies than people with a negative diagnostic test, and that these antibody levels were higher in people with secondary DENV infections. With this study, we show that detection of IgG4 antibodies against mosquito saliva may be a reliable method to evaluate the risk of dengue infection.

Aedes aegypti anti-salivary gland antibody concentration and dengue virus exposure history in healthy individuals living in an endemic area in Colombia.

INTRODUCTION: Mosquito salivary proteins are able to induce an antibody response that reflects the level of human-vector contact. IgG antibodies against dengue virus (DENV-IgG) are indicators of previous exposure. The risk of DENV transmission is not only associated to mosquito or dengue factors, but also to socioeconomic factors that may play an important role in the disease epidemiology. OBJECTIVE: To determine the effect of the presence of Aedes aegypti mosquitos in different stages in households and the history of dengue exposure on vector-human contact determined by the level of anti-salivary protein antibodies in people living in a Colombian endemic area. MATERIALS AND METHODS: A pilot study of 58 households and 55 human subjects was conducted in Norte de Santander, Colombia. A questionnaire for socioeconomic factors was administered and houses were examined for the presence of Ae. aegypti specimens in the aquatic stages. The level of DENV-IgG antibodies (DENV-IgG), in addition to IgG and IgM anti- Ae. aegypti salivary gland extract (SGE) antibodies (SGE-IgG, SGE-IgM) were evaluated by ELISA using blood collected in filter paper. RESULTS: We found a significant higher level of SGE-IgG antibodies in subjects living in houses with Ae. aegypti in aquatic stages. We also found a higher concentration of SGE-IgG antibodies in people exposed to DENV, a positive correlation between IgM-SGE and IgG-DENV and a negative correlation with IgG-SGE. CONCLUSION: Anti-salivary proteins antibodies are consistent with the presence of Ae. aegypti aquatic stages inside houses and DENV-IgG antibodies concentrations.

Use of anti-Aedes aegypti salivary extract antibody concentration to correlate risk of vector exposure and dengue transmission risk in Colombia.

Norte de Santander is a region in Colombia with a high incidence of dengue virus (DENV). In this study, we examined the serum concentration of anti-Aedes salivary gland extract (SGE) antibodies as a biomarker of DENV infection and transmission, and assessed the duration of anti-SGE antibody concentration after exposure to the vector ceased. We also determined whether SGE antibody concentration could differentiate between positive and negative DENV infected individuals and whether there are differences in exposure for each DENV serotype. We observed a significant decrease in the concentration of IgG antibodies at least 40 days after returning to an "Ae. aegypti-free" area. In addition, we found significantly higher anti-SGE IgG concentrations in DENV positive patients with some difference in exposure to mosquito bites among DENV serotypes. We conclude that the concentration of IgG antibodies against SGE is an accurate indicator of risk of dengue virus transmission and disease presence.