Fatty acid binding proteins (FABPs) are a family of proteins that bind and transport fatty acids and other hydrophobic ligands inside the cells. The Schistosoma mansoni Sm14 protein was the first FABP reported for helminthic parasites. Other FABPs from flukes with human and veterinary importance, including Fasciola hepatica, Schistosoma japonicum, Fasciola gigantica, Clonorchis sinensis, and Dirofilaria immitis are currently described and characterized (1).
Parasitic helminths cannot synthesize their own fatty acids and sterols, so they depend on their hosts for these essential nutrients. FABPs play a crucial role in facilitating the uptake and utilization of fatty acids from the host (1). FABPs may also participate in regulation of parasite development and differentiation (2), in the modulation of host immune responses and parasite survival (3), and in protection of worms against anthelmintic drugs (4).
For example, the arachidonic acid (ARA) plays an important role in the immune response against helminthic parasites, causing damage to the parasite’s skin, spines, and internal organs, and preventing the parasite from producing eggs (5). Sm14 can bind to ARA and prevent the action of this compound on S. mansoni. (6)
“Ribbons" diagram of the crystal structure of the Sm14 protein in complex with arachidonic acid, represented in "space fill". (PDB 1VYG).
FABP’s use as an antigen works by stimulating the host’s immune system to produce specific antibodies that can neutralize Sm14 functions (lipid transport and modulation of immune response), leading to the parasite’s death. This mechanism of action makes Sm14 the molecular basis for an effective vaccine against Fasciola hepatica infections in livestock.
The control of Fasciola hepatica infections in livestock (cattle, sheep, and goats) by a safe vaccine is an environmentally-friendly approach for improving food quality and safety that anticipates a sizeable economic impact.
Sm14 has shown promising capabilities against other helminth infections of veterinary importance, such as Dirofilaria immitis, which causes heartworm disease in dogs. Furthermore, the use of vaccines can reduce reliance on anthelmintic treatments, which can lead to parasite resistance. Overall, a vaccine such as Sm14 represents a significant advance in controlling parasitic infections in animals and can substantially improve animal health and productivity.
“Ribbons" diagram of the structural model of Dirofilaria immitis FABP
Product Development
LIVAC®: Sm14 vaccine for livestock formulated with specific adjuvant.
The global population of cattle, goats and sheep is around 4 billion animals.
Fasciolosis causes over 3 billion dollars in annual economic losses.
The current approach to the disease is still based on anthelmintic chemical drugs that ultimately contaminate meat, milk, and derivates with chemical residues.
The annual expenditure on these drugs in Europe is about 484 million dollars.
Scenario
– Widespread resistance to TCBZ, the most common anthelmintic drug.
– Global meat consumption expected to grow 73% by 2050.
– Global warming is expected to increase by 1.1 to 5.4 Celsius by 2100.
– Fasciolosis increases the emission of greenhouse gases by the affected animal by 10%.
Sm14PET: Sm14 vaccine for pets
The global market for flea, tick and heartworm products was estimated at USD 1.1. billion in 2022
1/3 of American dogs are treated each year against heartworm, at cost of 70 to 200 USD/year per 18kg dog.
Treating infected dogs costs between 1,200 and 1,800 USD
Scenario
– Canine infections in the US increased by 21,7% between 2013 and 2016, with an upward trend due to climate dynamics.
– Resistance to the main chemical treatment
Vaccines can be the game changer towards the prophylaxis of the liver fluke in livestock and of the heartworm in dogs.
development: vertyce↗