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The Universidad Nacional created the virus and it is hoped that the vaccine against bovine viral diarrhea will be successful. Photo: Víctor Manuel Holguín/Unimedios

Virus Created in the Laboratory Attacks Diarrhea in Cattle

May. 10 de 2012

By: Giovanni Clavijo, Unimedios

One animal virus and another human virus are combined to create a vaccine against bovine viral diarrhea. It has already been successfully tested in cellular cultures and will now be tested on live animals. The results are promising for the country's livestock sector.

Bovine viral diarrhea is an infectious disease that occurs during pregnancy and causes problems such as miscarriages or simply preventing pregnancy by causing the cows to go back into heat, thus decreasing the reproduction rate.

Its impact in the cattle–ranching sector can be seen in low meat and milk production rates. "It is estimated that reproductive diseases such as this virus (which is highly prevalent) cause annual losses of 44 billion pesos in this country", according to professor Jairo Jaime, coordinator of the research group in Microbiology and Epidemiology of the Veterinary and Zootechnics faculty at the Universidad Nacional de Colombia (National University of Colombia).

The disease reached Colombia in 1975, with a batch of calves imported from the Netherlands, whose clinical manifestations of the illness were subsequently confirmed by that country's government. In the 1990s, the research group at the UN, lead by professors Víctor Vera and Gloria Ramírez, for the first time determined the presence of antibodies against the virus in the blood streams of certain bovines.

There are three genotypes of bovine viral diarrhea and each one has variants called strains, which may or may not be cytopathic (meaning that they involve drastic alterations in the molecules). They are categorized as such due to their ability to damage or destroy cells in vitro, and the severity of the disease depends on the type of strain involved. The genotype classified as type I is the most widespread in Colombia and the one that causes the most reproductive problems. Genotypes II and III have less prevalence and have not yet been detected in this country.

The agent that causes viral bovine diarrhea is an RNA (ribonucleic acid) virus with a great capacity to transform itself in nature. It has been classified within the family of Flaviviridae viruses (generally transmitted by mosquitoes), which includes other animal viruses such as classical swine fever or hog cholera.

Types of vaccines

In Colombia, most vaccines used for animal health are imported. Because they are not made from isolated native strains, their effectiveness is uncertain. "We do not know if they protect the animals totally or partially", says a professor at the UN.

Traditionally they have been classified under two types: dead viruses and live viruses. The veterinarian affirms that the dead viruses do not multiply within the host, provide poor immunity and need to be applied more than once, which is why they are not optimum for use in production species.

The live virus vaccines, also known as attenuated, generate good immunity with just one dose, but are also problematic: "if the attenuation of the virus (reduction of its virulence) has not been stable, it could find a complimentary virus and reverse its pathogenic capacity to the point where it could cause the illness", says the coordinator of the research group at the UN.

The adenovirus

Beginning in 2007, the veterinarians were able to isolate the bovine diarrhea virus to study it in detail. "We analyzed its genome and isolated a gene from the protein called E2, which is responsible for the immunogenic response. We work on two versions of that protein and have inserted them into a type V human adenovirus (the adenoviruses are families of viruses that affect animals as well as humans). Subsequently, we evaluate its capacity for expression in cellular cultures (test tubes) and purify the virus with better activity, to then produce them on a large scale and test them on live animals (in mice)", according to Diana Susana Vargas, who developed this proposal for her master's thesis, under the direction of professor Jaime.

According to the researchers, the result was a recombinant virus, in other words, created from two different genetic materials. When used as a vaccine for bovines, it leads to a situation in which, while the viral diarrhea protein is expressed, the animals’ immune system produces antibodies that protect it from the pathogenic virus responsible for the disease.

From the test tubes, the adenovirus will be tested for its effectiveness in mice, using experimental models that will make it possible to also analyze the vaccine from the point of view of toxicity, protective doses and immunity, both of a cellular type as well as in the production of antibodies.

In this way, the Microbiology and Epidemiology group adapts technologies to conditions in the Colombian environment and enters into advanced research fields. According to Professor Jaime, "it involves a practical contribution to prevent a disease that has a great impact in the livestock sector".

Currently, this genetic therapy is used to treat cancer in humans and is progressively being implemented to develop vaccines. "It is possible that in the near future traditional pharmacological treatments would be replaced by corrections at the genetic or molecular level such as this one", concludes the researcher at the National University.+