Army
scientists and industry collaborators have successfully protected
laboratory animals from lethal hantavirus disease using a novel approach
that combines DNA vaccines and duck eggs. The work appears in a recent
edition of the online scientific journal PLoS ONE, published by the Public Library of Science.
According
to first author Jay W. Hooper of the U.S. Army Medical Research
Institute of Infectious Diseases (USAMRIID), this is the first time that
the DNA vaccine/duck egg system has been shown to produce an antiviral
product capable of protecting against hantavirus disease.
Hantavirus
causes a condition known as hantavirus pulmonary syndrome (HPS), which
has a case fatality rate of 35-40%. Currently there are no vaccines,
prophylactics, or therapeutics to prevent or treat this highly
pathogenic disease.
In
this study, the research team used a hamster model of Andes virus,
which is the predominant cause of HPS in South America and the only
hantavirus known to be transmitted person-to-person. Infection of Syrian
hamsters with Andes virus, as demonstrated in earlier studies at
USAMRIID, results in a disease that closely mimics human HPS in
incubation time, symptoms of respiratory distress, and disease
pathology. This makes it an ideal system for evaluating the feasibility
of postexposure protection strategies.
Collaborating
with Aldevron of Fargo, N.D. and the Universidad del Desarrollo in
Santiago, Chile, Hooper and his team first evaluated a natural product,
human polyclonal antibody, which was obtained as fresh frozen plasma
(FFP) from a patient who survived HPS. Their results indicate that FFP
shows promise as a post-exposure preventive treatment for HPS.
The
team then vaccinated ducks with a DNA vaccine against Andes virus. This
vaccine, initially developed and tested at USAMRIID, uses genetic
material, or DNA, that encodes a specific hantavirus gene to elicit an
immune response in the recipient.
Next,
they purified an antibody called IgY from the yolks of the duck eggs.
This purified IgY, as well as a similar version produced in duck eggs,
was capable of neutralizing Andes virus when tested in cell culture.
More importantly, it also protected Syrian hamsters from lethal HPS—even
when administered as a single injection several days after the hamsters
had been exposed to a lethal dose of virus.
The
work demonstrates the feasibility of using DNA vaccine technology,
coupled with the duck/egg system, to manufacture a product that could
supplement or replace FFP. Furthermore, the new approach can be scaled
as needed and eliminates the necessity of using blood products from HPS
survivors, which may be in limited supply.
According
to Hooper, another advantage of this technique is that duck IgY
naturally loses a part of the antibody that has been associated with
“serum sickness” when animal antibodies have been used in humans, making
the product potentially less reactogenic.
“This
antiviral product, if fully developed and manufactured, has the
potential to be used in future outbreak situations,” Hooper said. “It
also could be used to treat health care workers and others who have
close contact with HPS patients.”
In
addition, the authors suggest, the flexibility of the DNA vaccine/duck
egg system could be applied to the production of antibodies against
other infectious agents and toxins.
Source: U.S. Army Medical Research Institute of Infectious Diseases
