Avian influenza protection

The parallels between the current COVID-19 pandemic and past avian influenza (AI) outbreaks are not lost on Shayan Sharif. “In any pandemic, swift and measured actions are needed to contain and control the imminent spread. When a vaccine is available, the options change. And when a vaccine can be made more effective, progress is made,” says Sharif, associate dean of research and graduate studies at the Ontario Veterinary College at the University of Guelph.

Sharif led a multi-year research project looking at novel ways to prevent future AI outbreaks by boosting the immune response of the bird. The premise was that if the bird’s own immune system can rally to work in concert with a vaccine, then the level of disease protection provided will be stronger and more effective.

With no commercial AI vaccine currently available in Canada – and culling the only “treatment” option – the push for effective ways to protect birds is desperately needed. That’s where some of Sharif’s latest research comes in. He looked at immune-enhancing activities to protect birds against AI.

His research holds promise for a solution for Canadian poultry producers to prevent the disease. It also offers vital insights into technology that can boost a bird’s own immune system to be better equipped to fight off AI and other diseases.

Testing the potential of PAMPs
Sharif’s research looked at two avenues for helping birds build a stronger defence against disease, particularly AI. The first part of the study looked at how PAMPs – pathogen associated molecular patterns – could be used to boost immune response.

PAMPs are naturally occurring microbes that have been extensively studied for more than 20 years. They act as an adjuvant (or immune booster) and can be used with a vaccine or on their own to trigger a stronger response in birds.

When PAMPs are used with a vaccine, the vaccine must be a killed form, and that poses some challenges for the route of administration. Killed vaccines don’t always induce enough immune response on their own, and are most effective when injected – an impractical proposition in poultry production.

The search for a better solution led Sharif to nanoparticles as an effective carrier to administer killed vaccines with or without PAMPs.

“Nanoparticles are like tiny cages that can carry vaccine and PAMP molecules directly to target cells in the bird – respiratory or intestinal in the case of AI,” Sharif says. “They have been shown to boost the efficacy of vaccines and PAMPs, and are an effective vehicle for penetrating and integrating into target cells faster and more directly, delivering a better immune response for the bird.”

Sharif’s team searched for a PAMP that could deliver the best immunity. “We identified PAMPs with varying degrees of potency and efficacy and found one called CpG – which is microbial DNA – was the best for efficacy and immune response.”

Sharif’s work confirmed that nanoparticles work well to boost immune response and reduce virus shedding in birds. “There is a lot of promise for nanoparticles and vaccines in poultry and in people,” says Sharif. “In fact, it’s a technology that is being investigated in the current work on a coronavirus vaccine.”

Adenovirus as effective delivery vector
The second technology investigated for boosting immune response was the use of adenovirus as a biological carrier for AI vaccine. Sharif’s colleague Eva Nagy, avian virologist at OVC, led the team that discovered the efficacy of two particular adenoviruses as potential vehicles for delivering the vaccine antigen for AI and a variety of other vaccines.

Adenovirus works as a vector or delivery vehicle for vaccine. “A vector is like a car that can carry different passengers,” Sharif says. “In this case, an adenovirus vector may carry the key genes of avian influenza virus that when given to a chicken could confer immunity against the virus.”

Through the course of this research project, adenovirus 4 and 9 were licensed and commercialized with a Mexican vaccine company. While there has yet to be a commercial application for Canadian poultry producers, the opportunity is there.

“My hope is that in the near future we will be able to use vectors like adenovirus to carry bits and pieces of AI virus to be used as a vaccine,” Sharif says. The technology also has potential as a carrier for Newcastle and infectious bronchitis vaccines.

The commercialization question
Sharif knows nanotechnology holds tremendous promise for the Canadian poultry industry as a way to package killed vaccines. “If many of the poultry vaccines we use could be packaged in nanoparticles, we could deliver better efficacy,” says Sharif.

“And if we can commercialize adjuvants like PAMPs we can further enhance the immunity caused by vaccines.” And the routine use of nasal vaccines in Canada gives Sharif confidence that the nanotechnology would be an effective means to administer AI protection.

Sharif hopes to get the technology to market. Commercialization wasn’t part of this research project but his goal is to get it to market because of the tremendous potential it shows as an effective option for dealing with AI.

An exciting part of Sharif’s work on nanoparticles is that it doesn’t start and stop with protecting birds against another AI pandemic. It has potential for Newcastle, infectious bronchitis, Marek’s disease, Campylobacter and Clostridium perfringens – the latter microbe being the causal agent for necrotic enteritis.

For Sharif, the big question is how to move this work forward. “This is an open avenue for commercialization opportunities and I wish there were more options already available for Canadian poultry producers because we know that pandemics are a certainty. We can’t let our guard down. Influenza could have a comeback and we have to be ready.”