Andes virus (ANDV) and ANDV-like viruses are responsible for most
hantavirus pulmonary syndrome (HPS) cases in South America. Recent studies in Chile indicate that passive transfer of convalescent human plasma shows promise as a possible treatment for HPS. Unfortunately, availability of convalescent plasma from survivors of this lethal disease is very limited. We are interested in exploring the concept of using
DNA vaccine technology to produce
antiviral biologics, including polyclonal
neutralizing antibodies for use in humans. Geese produce
IgY and an alternatively spliced form, IgYΔFc, that can be purified at high concentrations from egg yolks.
IgY lacks the properties of mammalian Fc that make
antibodies produced in horses, sheep, and rabbits reactogenic in humans. Geese were vaccinated with an ANDV
DNA vaccine encoding the virus envelope
glycoproteins. All geese developed high-titer
neutralizing antibodies after the second vaccination, and maintained high-levels of
neutralizing antibodies as measured by a pseudovirion neutralization assay (PsVNA) for over 1 year. A booster vaccination resulted in extraordinarily high levels of
neutralizing antibodies (i.e., PsVNA80 titers >100,000). Analysis of
IgY and IgYΔFc by
epitope mapping show these
antibodies to be highly reactive to specific amino acid sequences of ANDV envelope
glycoproteins. We examined the protective efficacy of the goose-derived antibody in the hamster model of lethal HPS. α-ANDV
immune sera, or
IgY/IgYΔFc purified from eggs, were passively transferred to hamsters subcutaneously starting 5 days after an IM challenge with ANDV (25 LD50). Both
immune sera, and egg-derived purified
IgY/IgYΔFc, protected 8 of 8 and 7 of 8 hamsters, respectively. In contrast, all hamsters receiving
IgY/IgYΔFc purified from normal geese (n=8), or no-treatment (n=8), developed lethal HPS. These findings demonstrate that the
DNA vaccine/goose platform can be used to produce a candidate
antiviral biological product capable of preventing a lethal disease when administered post-exposure.