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Overview of swine research at VIDO


Areas of focus

I. Vaccines:
Post-weaning colibacillosis
Swine influenza
Porcine Respiratory and Reproductive Syndrome
Porcine circovirus

II. Formulation and Delivery:
Needle-free
Oral vaccination, mucosal immunization
Transcutaneous delivery
Viral and bacterial vectors

III. Innate immunity
Antimicrobial peptides
Novel immunomodulators (CpG, host defence peptides)

IV. Respiratory infections
Airway function, organic dust

V. Pig as model for human infections
Hepatitis C
Bordetella pertussis (whooping cough)
E. coli (traveller’s disease)
Influenza

VI. Technology Transfer
VIDO Swine Technical Group

Example 1: Post-weaning colibacillosis

Example 2: Vaccine formulation

Example 3: Needle-free delivery

Example 4: PRRS

Example 5: Respiratory infections

Example 6: Innate immunity

 

 

 

 

 

 

 


Example 1: Post-weaning colibacillosis

There are significant economic losses to global swine production due to post-weaning colibacillosis caused by E. coli bearing enterotoxigenic F4 fimbriae (ETEC). Fimbriae are appendages that allow the bacteria to attach themselves to other cells.

Prevention of disease depends on the creation of immune responses in the small intestine. Vaccines that could be delivered to this surface, called mucosal vaccines, are currently not available and treatment is limited to the use of antibiotics.

We are developing mucosal vaccines by using a "gut-loop" model in three-week-old piglets. Separate loops are surgically created in the jejunum of piglets, and vaccines are administered into each loop. Three weeks later, immune responses are studied by analyzing each loop.

This model allows analysis of immune responses at the intestinal surface in a living animal - the same environment that the vaccine must be effective in. Various vaccine formulations can be studied in only one animal.

The gut loop model allows researchers to visualize
the immune response at the intestinal surface for
different volumes of vaccine. This figure shows results
from different loops following immunization with varying doses of the F4 protein. Strength of the immune response
according to levels of IgG and IgA antibody-secreting-cells
was greatest for the 500 ug dosage.


Example 2: Vaccine formulation

Innate, or natural, immunity plays an important role in protecting pigs against various disease-causing organisms. Interestingly, many parts of the innate immune response are also potent immunomodulators that can be added to vaccines as adjuvants to boost immune responses, or can be used as stand-alone treatment for bacterial and viral infections.

These immunomodulating molecules cause the secretion of several key parts of the immune system such as cytokines and chemokines, that regulate immune cells such as B cells, T cells, NK cells, monocytes/macrophages and dendritic cells. Thus, these molecules can lead to the stimulation and enhancement of immune responses.

At VIDO, we are investigating the potential of these immunomodulators as adjuvants for a variety of vaccines or as stand-alone treatments against swine influenza.

Immunomodulators can cause the secretion of natural immune response molecules. This figure shows types and volumes of cytokines produced following immune cell stimulation with immunomodulators 1, 2 and 3.


Example 3: Needle-free delivery

A goal of modern vaccine research is the development of needle-free vaccine delivery strategies. VIDO is testing a variety of delivery systems for intradermal or transcutaneous application in livestock.

Immune responses at the mucosal surfaces are distinct from the immune responses that occur in the body as a whole. Delivery of vaccines to the mucosal surfaces (i.e. oral, intranasal) represents a potential strategy for creation of both mucosal and systemic (throughout the body) immunity. VIDO is investigating the mechanisms of mucosal immunity and vaccine formulations that can be delivered to the mucosal surfaces.

Intranasal device developed at VIDO and the University of Saskatchewan


Example 4: PRRS

Porcine respiratory and reproductive syndrome (PRRS) virus causes severe respiratory distress in young pigs and abortions in the last term of gestation. Current modified live and killed vaccines are sometimes successful, although differentiation between vaccinated and infected animals has been a challenge. In addition, live attenuated vaccines have resulted in the appearance of PRRS-like symptoms in sow herds and the altering of semen quality of boars.

We are developing PRRS vaccines based on a porcine adenovirus-3 vector system recently developed at VIDO. This system uses a live virus to deliver vaccines to the surfaces of the respiratory tract. The system allows the expression of foreign genes in adenoviral vectors, which ensures high expression of the foreign antigen and therefore induction of strong immunity against the foreign protein.We feel that such vaccines will be cost-effective and safe, with no risk of producing disease.

This figure shows how segments of the vector DNA can be replaced by genes coding for a PRRS antigen, for example. It is possible that these vaccines may be used to vaccinate against more than one disease.


Example 5: Respiratory infections

Airway function in swine can be affected by inhalation of organic dust or by bacterial or viral infection. Often, these are found together. To investigate the relationship between viral infections such as swine influenza and organic dust inhalation, we are using air chambers to analyze airway function. For example, we are analyzing the effect of lipopolysaccharide (LPS), an important membrane component of bacteria present in large quantities in dust, on the occurrence of viral infections. VIDO is the only organization in North America that examines the airway function in pigs using these air chambers.


Example 6: Innate immunity

Antimicrobial peptides (AMPs), also called host defence peptides, are small molecules found in virtually all life forms.

AMPs were originally called "nature's antibiotics" because of their potent antimicrobial activity. Research has demonstrated that these molecules are potent innate, or natural, immune system components with both antimicrobial and immuno-stimulatory function.

VIDO is investigating the use of AMPs against disease-causing organisms in pigs and the role of AMPs in respiratory infections. In particular, we are interested in the effects of stress, bacterial infections, and animal movement on the expression of AMPs. AMPs will also be used as vaccine adjuvants to create a broad and balanced immune response.

This figure shows the amount of the bacteria E. coli present after treatment with the antimicrobial peptide PG. After one hour of incubation with PG, all of the bacteria have been killed.


This figure shows the amount of the bacteria E. coli present after treatment with different volumes of the antimicrobial peptide PR-39. After one hour of incubation with 10 mg, 20 mg, or 50 mg of PR-39, all of the bacteria have been killed.


This figure shows the amount of the bacteria E. coli present after treatment with different volumes of the antimicrobial peptide PR-39. After six hours of incubation with PR-39, all of the bacteria have been killed.


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