From Pasteur to Proteq®: Latest Advances In Equine R&D

Louise Radford BVetMed. Cert.VR.MRCVS. DipM.MCIM, Equine Marketing and Technical Manager, Merial Animal Health Ltd

The recent launch of Merial’s updated EI vaccine ProteqFlu® sets a new landmark in the development of vaccines to protect the UK horse population against equine influenza.

Following guidance from the OIE Specialist Surveillance Panel urging manufacturers to update strains, the updated ProteqFlu® vaccine is the first to fully comply with the latest 2014 OIE recommended EIV strains. It makes ProteqFlu® the only equine flu vaccine updated to contain Richmond 07 and protect against the latest Florida sublineage Clade 2 strain.

Merial’s innovation in equine healthcare began more than 30 years ago when the company launched Eqvalan®, the first equine ivermectin based antiparasitic product of its generation, which was a major innovation in equine health. The recent launch of the updated ProteqFlu® vaccine is the latest product of an almost unrivalled heritage in leading edge technology.

Canarypox Vector Technology

Protection from influenza virus infection in humans and horses depends on both humoral and cell-mediated immune (CMI) responses. Antibodies neutralize the virus to prevent infection of cells and further spread of the virus.

The new ProteqFlu® contains two live recombinant canarypox viruses, vCP2242 and vCP3011, expressing the haemagglutinin (HA) gene from the equine influenza virus strains A/eq/Ohio/03 (Florida sublineage clade 1) and A/eq/Richmond/1/07 (Florida sublineage clade 2) respectively.

ProteqFlu® is the only equine influenza vaccine to use a recombinant viral vector technology. After inoculation the canarypox viruses enter the horse’s cells and the HA are expressed on the surface of these cells. This endogenous pathway, that closely mimics a natural infection, explains the rapid and strong humoral and cell-mediated immune responses triggered by vaccination with ProteqFlu®.

This results in a broad immune response, the ability to overcome maternal antibodies, and the ability to differentiate infected from vaccinated animals (DIVA).

Hervé Poulet, Head of BioDevelopment and BioResearch at Merial’s Lyon Laboratory summarises this latest advancement; “Merial has developed this strong and unique expertise in the development of non-replicative recombinant canarypox virus-vectored vaccines for various species and diseases, such as with feline leukaemia, rabies, equine influenza and West Nile virus.

“For the development of ProteqFlu®, our non-replicative recombinant canarypox vector expressing the EI virus HA is used because of its ability to induce a broad immune response, including a strong cellular immunity which is an essential component in protecting against this highly contagious disease.”

GastroGard®. Another first!

Merial has continued its path of leading edge healthcare for horses in the areas of West Nile virus vaccine, cox-hib non-steroidal pain management, and prevention and treatment of gastric ulcers.

Equine Gastric Ulcer Syndrome (EGUS) is a painful, threatening condition that can affect horses of all ages, breeds and disciplines¹. The chances of a horse developing a gastric ulcer is more than one in three, and nearly two in three performance horses could be suffering from gastric ulcers²-⁴.

Omeprazole Technology

Omeprazole is a potent inhibitor of gastric acid secretion and has prolonged anti-secretory effect, allowing once daily dosing. The product formulation used is very important, as the active ingredient itself is easily degraded by stomach acid. Extensive research was conducted to create the patented formulation of GastroGard® important for the palatability, passage, and bioavailability of the active ingredient.

For the treatment of gastric ulcers in humans, to prevent the stomach acid from degrading the omeprazole, the granules are coated to make them acid resistant. They are also protected by a gelatine capsule, which is swallowed whole. It is obviously impossible to prevent a horse from chewing and destroying the capsule, therefore these are not an appropriate form of drug delivery for horses.

The paste formulation of GastroGard® however, has a protective effect which allows the omeprazole to pass through the stomach and be absorbed in the small intestine and taken up into the bloodstream. It also enables once daily administration.

Not all omeprazole paste preparations are equivalent either. To enable healing of gastric ulcers, there must be a significant increase in the pH of the gastric fluid, and this must also be maintained for sufficient periods of time. A pH greater than 4 is considered necessary for healing of lesions and resolution of clinical signs.

In conclusion, it is important to be sure that the treatment you are using is actually a veterinary licensed formulation, and whether effective studies have been performed to prove this. It is also important to be aware of detection and withdrawal times - an ineffective medication with a prolonged detection time could be a costly mistake.

From Pasteur to Proteq®

Merial’s vaccine heritage began in 1857 with Louis Pasteur, when he proved a link between infections and micro-organisms. It was much later, in 1880 when Pasteur made the first rabies vaccine, and it was another fourteen years later when Marcel Mérieux joined the Institut Pasteur as assistant, that Merial’s vaccine heritage truly began.

In 1897 Mérieux established the Institut Biologique Mérieux, an analytical production laboratory and it was his son Charles who, in 1937 succeeded his father and developed the first vaccine against foot-and-mouth disease.

Further developments continued; 

1967-1968: Alain Mérieux succeeds his father and sells 51% stake to Rhône-Poulenc

1985-1989: Institut Mérieux forms an alliance with Institut Pasteur, and acquires Connaught Laboratories (Canada/US) to become the world’s leader in vaccines

1994: Rhone-Poulenc buys remaining 49% stake of Pasteur Mérieux Connaught

1999: Formation of Aventis (50% Rhône-Poulenc, 50% Hoechst), and Pasteur Mérieux Connaught becomes Aventis-Pasteur

1999: Formation of Merial (50% Merck, 50% Aventis), which became Europe’s largest animal vaccine manufacturer

1999: Merial (USA) launch Purevax® Rabies for cats, Purevax® Distemper for Ferrets, Recombitek for dogs.

2003: Merial (UK) launched ProteqFlu®, the first, and still the only the only EI vaccine to use recombinant canarypox vector technology

 

References

1. Radostits OM, et al. Veterinary Medicine: A textbook of the diseases of cattle, horses, sheep, pigs and goats. Philadelphia: WB Saunders Co.; 2007:237-241.

2. Murray MJ, Grodinsky C, Anderson CW, Radue PF et al. Gastric ulcers in horses: A comparison of endoscopic findings in horses with and without clinical signs. Equine Vet J 1989;7(suppl):68-72.

3. Mitchell RD. Prevalence of gastric ulcers in hunter/jumper and dressage horses evaluated for poor performance. In: Proceedings of the Association of Equine Sports Medicine Annual Meeting 2001.

4. Nieto JE, Snyder JR, Beldomenico P, Aleman M, Kerr JW, Spier SJ. Prevalence of gastric ulcers in endurance horses – a preliminary report. Vet J 2004 Jan;167(1):33-37.

 

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