Download New antibodies may help treat “shipping fever” in cattle

New antibodies may help treat “shipping
fever” in cattle
What is this research about?
Bovine respiratory disease complex (BRDC) is
a potentially fatal disease in cattle that results
from having multiple bacterial and viral infections at the same time. “Shipping fever”, as
BRDC is known to most cattle producers, gets
its nickname from the fact that cattle are most
vulnerable during the stressful and crowded
situations that are created when they are being transported. Bovine herpesvirus type 1
(BoHV-1) is one of the viruses that may contribute to shipping fever, and is also responsible for infections of the respiratory and reproductive systems of cattle. Shipping fever alone
costs the U.S. cattle industry up to $3 billion
dollars a year. Since the existing vaccines
against BoHV-1 do not provide full protection,
giving cattle antibodies against the virus are
likely to be helpful. Antibodies are small proteins made by the cells of the immune system,
which help the body to recognize a virus or
virus-infected cell and attack the virus.
Keywords:
Cattle, bovines, herpes virus, antibody, vaccine, shipping fever, bovine respiratory disease complex (BRDC)
What did the researchers do?
The researchers took the genetic material from
a cell that was producing BoHV-1 antibodies,
and made small changes to the specific gene for
the antibody. After making many copies of this
new gene, an electric current was used to introduce these copies into new cells. For this second step, the single-celled organism called
Pichia pastoris was used. Next, the antibodies
that were produced by the P. pastoris cells
were isolated. To determine how well these
antibodies could attack BoHV-1 viruses, the researchers then added the antibody to infected
cells to assess their attacking ability.
What you need to know:
Some antibodies against bovine herpesvirus type-1 have the ability to join together
into groups of two or more, which were
found to be much more effective at recognizing and attacking virus-infected cells
than single antibodies were. These new
antibodies may help treat bovine respiratory disease complex and “shipping fever”
in cattle.
Project supported by:
A program of the
OMAFRA-U of G
Partnership.
What did the researchers find?
The antibodies isolated from the P. pastoris
cells were not all identical, due to changes
that occurred after the antibodies were created. Some antibodies had parts cleaved (cut
off), some had small sugar molecules added,
and some naturally joined together into
groups of two or more antibodies. These
groups of antibodies, called multimers, were
effective at recognizing and attacking BoHV1 viruses in the living cells. In fact, they were
twice as effective as single antibodies
(monomers). The variation in attached sugar
molecules, however, did not seem to impact
the effectiveness of an antibody.
How can you use this research?
Veterinary scientists can use these effective
antibodies against bovine herpesvirus type 1,
along with more cost-effective ways to control
and eradicate BoHV-1 infection.
Cattle producers can use this research to
identify new and potentially more effective
ways to treat and control BoHV-1 infections
and “shipping fever”.
Article citation:
Pasman, Y., Nagy, E., & Kaushik, A.K. (2012).
Enhanced Bovine Herpesvirus Type 1 Neutralization by Multimerized Single-Chain Variable
Antibody Fragments Regardless of Differential
Glycosylation. Clinical and Vaccine Immunology, 19(8), 1150-1157.
About the University of Guelph
researchers:
Principal Investigator: Azad Kaushik is an Associate Professor in the Department of Molecular
and Cellular Biology at the University of Guelph.
Email: [email protected].
Graduate Student: Yfke Pasman Email:
[email protected]
Collaborator: Eva Nagy is a Professor in the Department of Pathobiology at the University of
Guelph. Email: [email protected].
Cite this work:
University of Guelph, Institute for Community
Engaged Scholarship (2012). New antibodies
may help treat “shipping fever” in cattle. Retrieved from:
http://hdl.handle.net/10214/5654
This summary is a project of the Institute for
Community Engaged Scholarship (ICES) at the
University of Guelph, with project partners:
the Catalyst Centre, SPARK Program at the
University of Guelph, and the Knowledge Mobilization Unit at York University. This project
is part of the Pan-Canadian Research Impact
Network.
http://csahs.uoguelph.ca/pps/Clear_Research
This work is licensed under the Creative Commons Attribution-NoDerivs 3.0 Unported
Single mutation can affect antibody’s ability to
bind to and neutralize bovine herpes virus
What is this research about?
As part of its defence against disease-causing
organisms, the immune system produces complex proteins called antibodies that can recognize, attach to, and neutralize bacteria and viruses. Binding to the virus or bacteria takes
place at a site on the antibody made up of two
different protein chains, called the heavy
chain (VH) and light chain (VL). Both parts are
needed for the antibody to be effective.
Through genetic engineering, researchers
have developed whole antibodies that are capable of fighting various viruses and bacteria.
Unfortunately, the large size of these antibodies makes it hard for them to get to the site of
infection. To overcome this problem, scientists are now looking at creating smaller antibody fragments, called single chain variable
fragments (scFv), which can bind to the virus
or bacteria but also move more easily through
the body. In scFv, the heavy and light chains
are connected by a very short linker made up
of around 12 amino acids. Longer linkers may
allow scFv to work individually, while shorter
linkers may require two matching scFv to join
together to function.
What did the researchers do?
The researchers used a single chain variable
fragment (scFv) that was able to bind to and
neutralize bovine herpes virus type 1 (BoHV1), a causative agent of respiratory and genital
diseases in cattle. Through genetic engineering,
this scFv was modified to have an 18 amino acid linker (scFv3-18L). A nearly identical scFv
was also created that had a single mutation in
part of the heavy chain - this mutant version
was called scFv4m-18 L. Next, researchers tested the ability of both antibody fragments to
recognize, bind to, and neutralize BoHV-1 in
infected cells grown in the laboratory, compared to an antibody fragment with a 7 amino
acid linker (scFv1-7L).
What you need to know:
Genetically engineered antibody fragments, working either individually or in
pairs, were able to effectively bind to and
neutralize bovine herpes virus type-1 in
infected cells. A single mutation affected
the antibody fragment’s ability to neutralize the virus, without changing its ability
to recognize and attach to it.
Project supported by:
A program of the
OMAFRA-U of G
Partnership.
What did the researchers find?
The antibody fragment scFv3-18L was able to
recognize and bind to BoHV-1, as well as neutralize BoHV-1 in infected cells. A dose of 0.18
μM (micromolar) of scFv3-18L resulted in
more than 50% viral neutralization, compared
to a dose of 0.1 μM of scFv1-7L for the same
effect. Therefore, linker size affected an antibody fragment’s ability to neutralize the virus.
The mutated fragment, scFv4m-18L, was also
able to neutralize the virus, but the required
dose was nearly three times greater. The mutation did not, however, affect the ability of
scFv4m-18L to bind to the virus.
How can you use this research?
Vaccine scientists can use this research to
better understand how antibody binding and
viral neutralization can be affected by a single
mutation.
Vaccine developers can further this research
by continuing to develop single chain variable
fragment (scFv) antibodies against a wide
range of viruses and bacteria that infect humans and animals, for the purposes of developing vaccines or diagnostic tests.
Article citation:
Koti, M., Nagy, E., & Kaushik, A.K. (2011). A single point mutation in framework region 3 of
heavy chain affects viral neutralization dynamics of single-chain Fv against bovine herpes
virus type 1. Vaccine, 29, 7905-7912.
About the University of Guelph
researchers:
Principal Investigator: Azad Kaushik is an Associate Professor in the Department of Molecular
and Cellular Biology at the University of Guelph.
Email: [email protected].
Graduate Student: M. Koti Email:
[email protected]
Collaborator: Eva Nagy is a Professor in the Department of Pathobiology at the University of
Guelph. Email: [email protected].
Keywords:
Vaccines, antibodies, bovine herpes virus 1,
virus neutralization, point mutation, amino acid linker, single-chain variable fragment
Cite this work:
University of Guelph, Institute for Community
Engaged Scholarship (2012). Single mutation
can affect antibody’s ability to bind to and neutralize bovine herpes virus. Retrieved from:
http://hdl.handle.net/10214/5653
This summary is a project of the Institute for
Community Engaged Scholarship (ICES) at the
University of Guelph, with project partners:
the Catalyst Centre, SPARK Program at the
University of Guelph, and the Knowledge Mobilization Unit at York University. This project
is part of the Pan-Canadian Research Impact
Network.
http://csahs.uoguelph.ca/pps/Clear_Research
This work is licensed under the Creative Commons Attribution-NoDerivs 3.0 Unported