Antiviral Biologic Produced in DNA Vaccine/Goose Platform Protects Hamsters Against Hantavirus Pulmonary Syndrome When Administered Post-exposure

被引：30

作者：

Haese, Nicole ^{[1
]}

Brocato, Rebecca L. ^{[2
]}

Henderson, Thomas ^{[1
]}

Nilles, Matthew L. ^{[1
]}

Kwilas, Steve A. ^{[2
]}

Josleyn, Matthew D. ^{[2
]}

Hammerbeck, Christopher D. ^{[2
]}

Schiltz, James ^{[3
]}

Royals, Michael ^{[4
]}

Ballantyne, John ^{[5
]}

Hooper, Jay W. ^{[2
]}

Bradley, David S. ^{[1
]}

机构：

[1] Univ N Dakota, Sch Med & Hlth Sci, Dept Basic Sci, Grand Forks, ND 58201 USA

[2] US States Army Med Res Inst Infect Dis, Div Virol, Ft Detrick, MD USA

[3] Avianax LLC, Grand Forks, ND USA

[4] Cedar Ind, Pierce, CO USA

[5] Aldevron, Fargo, ND USA

来源：

PLOS NEGLECTED TROPICAL DISEASES | 2015年 / 9卷 / 06期

关键词：

CHICKEN EGG-YOLK; PSEUDOMONAS-AERUGINOSA INFECTIONS; HUMORAL IMMUNE-RESPONSES; LETHAL DISEASE-MODEL; ANDES VIRUS; NEUTRALIZING ANTIBODIES; SYRIAN-HAMSTERS; IGY; IMMUNOGLOBULINS; VACCINATION;

D O I：

10.1371/journal.pntd.0003803

中图分类号：

R51 [传染病];

学科分类号：

100401 ;

摘要：

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 IgY Delta Fc 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. PsVNA(80) titers > 100,000). Analysis of IgY and IgY Delta Fc 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. alpha-ANDV immune sera or IgY/IgY Delta Fc 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/IgY Delta Fc protected 8 of 8 and 7 of 8 hamsters respectively. In contrast all hamsters receiving IgY/IgY Delta Fc 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.

引用

页数：19