Dengue NS1-specific IgY antibodies neutralizes dengue infection without inducing antibody dependent enhancement.

Abstract

Abstract Dengue virus (DENV) is the most prevalent arbovirus with worldwide cases increasing from 2.2 to 3.2 million in the last 5 years. Symptoms of DENV infection range from a mild fever to extensive vasculature permeability resulting in hemorrhagic fever and shock. Passive and active vaccines have been unsuccessful in protecting from or treatment for DENV infection because of antibody dependent enhancement (ADE), increased viral load due to increased monocyte opsonization by non-neutralizing Abs from a different DENV serotype. We have previously demonstrated that polyclonal avian IgY generated against whole, killed DENV-2 ameliorates DENV infection in mice without ADE. The lack of ADE with therapeutic IgY supported our hypothesis that IgY may provide a viable treatment for DENV infection as mammalian Fc receptors are unable to bind to IgY. Here we isolated DENV epitope-specific IgY and test these purified IgY pools for their ability to neutralize DENV in vitro. Avian IgY specific for Non-Structural-1 (NS1) demonstrated neutralization capacity in vitro equal to the whole polyclonal DENV IgY preparation. DENV-NS3 specific IgY, on the other hand, did not demonstrate any neutralization of DENV in vitro. We propose that NS1-specific IgY may provide a viable oligoclonal treatment for DENV infection in humans without inducing ADE.