| Universiti Putra Malaysia

Innovation in Live Attenuated Fowl Adenovirus (FAdV) CRISPR-based vaccine to protect chickens from IBH disease

A team of researchers from Universiti Putra Malaysia (UPM) has successfully developed the Live attenuated Fowl Adenovirus (FAdV), a CRISPR-based vaccine which is able to elicit high antibody titer against FAdV infection, easily administered to chickens, and protect against Inclusion Body Hepatitis (IBH). 

This innovation contains special features at the genotype sequences of the fowl adenovirus developed innovatively by reducing the need for continuous transfer for viral attenuation, which indirectly reduces the cost and duration of production time. This special feature makes it less virulent, immunogenic, and feasible for use in most countries affected by the fowl adenovirus.

This innovation also offers orally administered vaccine, and the large-scale preparation is easy to handle, indirectly reducing cost and preparation time in farms.  

FAdV is the etiological agent of IBH disease. IBH is a predominant viral disease of FAdV, which causes substantial economic loss to poultry farms.

The global epidemiology of the disease was reported in the Asian continents since 1963. The first case of IBH in Malaysia was reported in 2005 with high mortality and poor performance profile due to FAdV infection. Since then, the disease had been reported in major poultry farms across several states in Malaysia and remained a significant threat.

Head of the research team, Assoc. Prof. Dr. Nurulfiza Mat Isa, said the Live attenuated Fowl Adenovirus (FAdV) CRISPR-based vaccine involved modification of the virus fibre protein, hence alters the genotype sequence of FAdV into a less virulent, genetically stable, immunogenic, and feasible vaccine to be applied in countries with FAdV infection.

She said the Live attenuated Fowl Adenovirus CRISPR-based vaccine is a modified wild type virulent, Fowl Adenovirus UPMT27 strain that has been physically mutated, contributing to the non-proper functioning of its fibre protein. 

“This modified fowl adenovirus was the result of genome editing using CRISPR technology in primary chicken liver cells, which are validated, harvested, and propagated in SPF embryonated chicken eggs for further commercialization,” she said.

She added that the weakened vaccine can be administered orally and is easily carried to the stomach via the alimentary canal for processing.

It is produced in powder form and needs to be mixed with water for consumption, and it can be given to a one-day-old chick. One feeding or dose is sufficient for each chicken.

The early entry of the live attenuated fowl adenovirus CRISPR-based vaccine into cells depends on the interaction of fibre protein adhesion with host cells receptor. Modifications of the fowl adenovirus fibre protein will interfere with the function of the protein and in turn affect the imperfect host-pathogen interactions,” she said.

She said this would allow time and enable the host cells to elicit more antibodies against the fowl adenovirus due to its weak internalization and neutralization activities.

She said that this invention involves using the CRISPR technology to produce weakened attenuated viruses rather than the conventional methods, which are time-consuming, costly, and prone to technical errors.

“This vaccine is easy and cost-effective to produce and suitable for industrial application,” she said.

Dr. Nurulfiza said the vaccine features offer advantages compared to existing commercial vaccines in the current market.

According to her, the disadvantages of the existing technology in developing the fowl adenovirus vaccine include cloning the antigenic fragment, which may cause toxicity of recombination and subunit vaccine types; incomplete inactivation, undefined amounts of antigen, and parenteral application require extensive handling procedures of inactivated vaccine. 

Apart from her, the other research team members are Prof. Dato’ Dr. Mohd Hair Bejo, Prof. Dr. Abdul Rahman Omar, Prof. Datin Paduka Dr. Aini Ideris, Assoc. Prof. Dr. Mariatulqabtiah Abdul Razak, and Salisu Ahmed.

The innovation began in March 2018 and ended in December 2020, and the product is patented. The product won the gold medal at the International Expo on Inventions and Innovations – Malaysia Technology Expo (MTE) 2021. – UPM

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