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“Our short-term goal is to produce more goats by breeding,
collect the milk, purify the protein, produce the vaccine, and
test its efficacy,” Westhusin said. Another goal, he said, is to start
clinical trials with nonhuman primates before potentially proceeding
with human trials.
There are, of course, many challenges in accomplishing the
project. There are several serotypes or strains of malaria and
each protein needs to be tested to determine which is the most
effective.
Along the way, researchers need to find the most effective and
efficient technologies to produce GM animals. Options include
inserting a transgene into a one-cell embryo by micromanipulation
versus using nuclear transfer technologies. Perhaps the
biggest challenge is to raise the funds to take the project further,
as all the research to date has been funded by pooled resources,
and no designated source of funding has been available for the
project.
“We could really use some ‘angel funding’ for this project,”
Westhusin said.
Westhusin and Long both say that there is great potential for
this research, as biopharmaceuticals produced by GM animals
comprise an up-and-coming industry.
“Products from GM animals, such as cows, goats, and pigs,
whether it is a drug, protein, or a pharmaceutical product, are
going to become commonplace just like how GM crops are now,”
Westhusin said. “Potentially, producing a million doses of vaccine
S
Salmonella infection, or salmonellosis, is a major public health
problem that carries a substantial price tag. Recent news stories
about outbreaks of salmonellosis have harmed industries. Historically,
pigs and the consumption of salmonella-contaminated
pork have been a major source for the transmission of this
disease to humans. To better control human exposure to and
infection by this pathogen, it is important to better understand
the swine host-pathogen relationship by developing better detection
measures.
Scientists at Texas A&M College of Veterinary Medicine &
Biomedical Sciences (CVM), in collaboration with researchers
at the Swedish National Veterinary Institute and the Swedish
University of Agricultural Sciences, have examined the intermittent
pattern in which pigs shed salmonella bacteria in their feces.
They discovered that salmonella may lay dormant in the host
at an undetectable level as a survival strategy that prolongs the
host’s infection. Furthermore, different salmonella serotypes are
shed and go dormant at different frequencies, making detection
especially difficult. The results of this research were recently
published in the journal PLoS ONE.
This “off and on” pattern of pathogen excretion can lead to a
host being misdiagnosed as clear of bacteria when in fact it is still
infected. In either case, pigs typically do not show physical signs
of being infected. In the “on stage,” the host sheds the bacteria
in fecal material, whereas in the “off stage,” the pathogen is still
present in the host, but is not shed. Therefore, the leading method
of detecting infection—fecal shedding—becomes difficult.
“Because of the important role that pigs have played in salmonellosis
outbreaks in other pigs and humans, reliable detection
measures and models are critical in developing efficient salmonella
control efforts,” said Dr. Renata Ivanek-Miojevic, assistant
professor of epidemiology in the Department of Veterinary Integrative
Biosciences. Although this early study has documented
the ability of salmonella to lay dormant, thereby extending its
in one goat can avoid the need for having more common facilities
that can cost hundreds of millions of dollars,” he said. “Our
long-term goal is to deliver products like vaccines or nutraceuticals
orally in the milk of goats, a kind of fortified milk that children
in developing countries can drink to receive vaccines and
other medicines. We could have a living bioreactor on the farm
delivering beneficial proteins, nutraceuticals, and medicines very
cheaply.”
In efforts to reach this goal, Westhusin and Long are especially
grateful for the support from their research team. “We love our
team. They are like a family,” Westhusin said. He credited Long,
who has worked with him for over two decades; Dr. Mike Golding,
an assistant professor at the CVM; and his mentor, Kraemer.
“It’s very rewarding to work with a dedicated group of people
who share a similar vision of long-term goals that could potentially
change the world and have a major impact on human
health and welfare,” Westhusin said.
Dr. Glen Laine, professor and head of the department of Veterinary
Physiology and Pharmacology praised this research.
“This is another example of the One Health Initiative. Drs.
Westhusin’s and Long’s discoveries are having a profound impact
in the way in which people are vaccinated and protected against
deadly, infectious diseases. Their malaria work at the CVM will
prevent the suffering of countless children around the world,” he
said.
Texas A&M Research Unlocks Mystery of
Salmonella Infection
presence in the infected host,
future research will investigate
whether the same association
between the cyclic behavior and
the length of infection holds
true in other host-pathogen
models.
“With this study, we were
able to observe the relationship
between shedding pattern and
length of infection in several
serotypes of salmonella in the Dr. Renata Ivanek-Miojevic
swine host,” Ivanek said. “From here, we will need to use what
we learned and the models that we were able to develop to see if
the same behavior is observed in other host-pathogen systems. If
so, the relationship may be useful not only in improving detection
methods but also in understanding evolutionary ecology of
this and similar infectious diseases with an ‘off and on’ pattern
of pathogen excretion and consequently adopting better control
measures.”
This study, funded by the National Science Foundation, will
become a model for future studies aimed at furthering the detection
capabilities and effective control for salmonella and similar
infectious agents in their animal and human host populations.
Dr. Evelyn Tiffany-Castiglioni, professor and head of the
department of Veterinary Integrative Biosciences said, “Dr.
Ivanek is among an elite group of veterinarians who are creating
new mathematical models to understand how infectious organisms
evolve in their hosts and in the environment to survive and
spread. Her research is exceptionally creative in bringing together
different disciplines of science, statistics, and mathematics
to help predict outbreaks of Salmonella infections. It reflects a
very clear appreciation of the concept that human health, animal
health, and ecosystem health are inextricably linked.”
CVM Today • Winter 2012 • 19