GRONINGEN 2022

NANOBUDDY

A Novel Nanotherapeutic Prevention Strategy Against Highly Pathogenic Avian Influenza.

INTRODUCING

A Novel Nanotherapeutic Prevention Strategy Against Highly Pathogenic Avian Influenza.

The Netherlands suffers from uncontrollable avian influenza outbreaks

The highly pathogenic avian influenza virus (H5N1) is raging throughout the world. In the 2021/2022 flu season, the Netherlands experienced the largest number of outbreaks ever recorded in the poultry industry.

Current measures fail to prevent outbreaks in the poultry industry

Vaccination strategies are currently unemployable due to the restrictions put on exporting vaccinated meat. Therefore, preventing further spread of the virus can only be done through transport restrictions, or (preventively) culling and caging chickens.

In the 2021/2022 flu season alone, 4.078.700 Dutch birds have been culled to prevent spread in the poultry industry (updated until September, 2022)

Even though this number is already huge, this is only a fraction of the 77 million chickens culled chickens worldwide (updated until May, 2022) [2]

The highly pathogenic avian influenza virus

Highly pathogenic avian influenza is an extremely contagious, multi-organ systemic disease leading to high mortality in poultry and wild bird populations. It is caused by some H5 and H7 subtypes of type A influenza virus [3].

The disease might transmit to humans through zoonosis

Immunologists are sounding the alarm bells that the disease might jump to humans if left uncontrolled [5].

Avian flu seasons are increasingly more impactful on poultry, as well as wild birds each year.

Outbreaks increase in frequency and severity in not just the Netherlands, but around the whole world. Besides the millions of culled poultry in the industry, 400.000 non-poultry birds have died as a result of the virus: twide the numbers reported in the last ‘major’ wave [2, 4].

Rapidly increasing numbers of animals and people are affected, while there is no solution ready to be implemented. Therefore, we set out to find a biosynthetic solution to combat avian influenza outbreaks in the poultry industry.

INTRODUCING

Step 1: Engineer our Nanobuddies

Engineer Limosilactobacillus reuteri, a chicken lung and gastrointestinal probiotic, to secrete a nanotherapeutic which can deactivate the highly pathogenic avian influenza virus.

Step 2: Spray:
Our Nanobuddies enter the poultry

Spray poultry with a solution containing our genetically modified L. reuteri. Upon entering the poultry, these bacteria will start to inhabit the mucus layer of the poultry lungs and gastrointestinal systems.

Step 3: Nanobody secretion at viral transmission hotspots

Our Nanobuddies will start to secrete a protective layer of nanobodies at locations where viral transmission most often occurs. These nanobodies can target and deactivate the virus, preventing it from entering the cells of the chickens.

Step 4: Viral blocking

The nanotherapeuthic that our Nanobuddies produce will accumulate in poultry microbiomes, ready to bind to avian influenza virus particles that they can broadly bind to: namely, the highly pathogenic avian influenza H5N1 variant.

Step 5: Biocontainment

Upon leaving the spray solution, the biocontainment strategy gets activated. Once our Nanobuddies have entered poultry, the bacteria will not be likely to escape anymore. Through a temperature and light sensitive CRISPR-Cas based kill-switch, we engineered our bacteria so that they will be killed when escaping the poultry.

Protecting our feathery friends!

The avian influenza crisis has never been more relevant than right now. Especially since there are currently no solutions that can deal with this problem with the proper magnitude. This problem involves a lot of different stakeholders, perspectives, needs, and safety concerns. With Nanobuddy, we therefore aimed to create a safe, responsible, and most importantly: effective solution to the avian influenza crisis in the poultry industry, to save millions of needlessly culled poultry lives.