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The EPM Vaccine Debate

A vaccine for EPM must be effective, affordable, and enter into the development pipeline. 

Will a commercial vaccine be developed?

There are some considerations before one undertakes the estimated 5 million dollar project to prove a vaccine is safe and effective.  The return on investment must hit $50 million/year.  EPM is a rare disease and is unlikely to raise the interest of big pharmaceutical companies; even $20 million/year projects are non-starters.  As animal drug companies merge, less profitable projects are scrapped making it more important to support your local small research entities developing novel drugs and vaccines!

What vaccine for EPM is affordable?

How about free?  And available to those that need it?  We have an idea.

Understanding coccidiosis can lead to understanding how to induce protective immunity without causing drug resistance.

  • In mice it was shown that some (not all) drugs can prevent protozoan parasites entering neural tissues but when no protective immunity develops, removing  the animals from drugs allow them to succumb to disease.

 

  • Eimeria causes diarrhea in baby chickens.  Protective immunity is induced by feeding day old chicks a mutant Eimeria (mutated by shortening the parasites sexual cycle).  The organisms that cause EPM and EMS (muscular sarcocystosis due to S fayeri) require two hosts.  Is the same protective immunity initiated when asexual stages are used for horse vaccines?

 

  • Sarcocystis neurona and S fayeri are coccidian parasites that use two hosts, the horse is the intermediate host affected by the asexual stages of the parasite. There is an indication that protection is possible. Consider this, overwhelmingly more horses have antibodies against S neurona than those that show clinical disease.  Serum antibodies to disease ratio is 100:1. Elucidating why that one horse gets disease is a later subject, right now we want to know if we can show protective immunity with exposure.   What is good evidence that infectious oocysts shed by the opossum—> ingested by horses followed by releasing asexual stages, can protect a horse against EPM?

 

  • In 2004 horses were given overwhelming S neurona challenge with oocysts that were collected from opossums.  The infected horses were subjected to stress.  Stressed horses showed some clinical signs (sarcocystosis) but they did not get EPM (no organisms were ever found in the brain tissues). When the experiment was repeated with extra stress after infection, these horses didn’t get sicker, they got better!  The horses recovered!

 

  • In a “prevention” study in which horses were given Marquis daily, followed by oocyst challenge, horses got clinical disease and did not produce immune antibodies.  The authors concluded this drug didn’t prevent disease.  Other drugs in the same class would be expected to show similar results.

 

  • In 2009 we showed that a vaccine could work in vivo (in the live horse).  Vaccinating horses with the surface protein expressed by the asexual merozoites found in brains of EPM horses protected them against S neurona challenge. It didn’t protect them against some very mild early signs of initial inflammation from challenge. However, vaccinated horses did not show clinical disease (ataxia) while the unvaccinated, controls did get disease.  To avoid infecting more horses, we designed an in vitro (laboratory) experiment using immune cells from the blood stream of the vaccinated and control horses.  We found out that our vaccine didn’t induce the right kind of immunity against other strains of neurona, the only protection was against the vaccine strain.  This means any vaccine would need to be multivalent and contain proteins from all S neurona the horse would potentially contact.  Interestingly, once the monovalent-vaccinated horses were challenged with a live organisms (same strain), they were protected against all strains

The take home message is that low dose exposure found in contaminated environments contain the strains that protect horses most of the time, just like the baby chickens.  Protective immunity elicited by environmental exposure in one environment won’t necessarily protect a horse when it moves to a new environment.  Most horses will do well with environmental exposure so long as they don’t get drugs that prevent immunity to develop.  It will be necessary to identify that one horse in 100 that will develop a dysregulated inflammatory response.  We can do that with testing.  Some of our studies measure protective immunity, the best methods to elicit the right kind of immunity, and to identify the molecular target that allows one horse not to become immune. 

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