Pathogenes Inc associates infection with S. neurona strain SAG 1 with polyneuropathies. Two horse studies provides evidence.
The killed S. neurona Fort Dodge vaccine (the vaccine was manufactured by growing SN2, a SAG 1 strain of the protozoa) caused clinical signs in horses. Some people thought that the vaccine caused "EPM", but this was impossible...the organism was killed. And EPM is the presence of parasites in the central nervous system. If you looked at the vaccine under the microscope, as we did, the organisms were visible. What concerned us was the presence of numerous equine dermal cells, the cells used to culture the organisms. The model for experimental allergic neuritis (PNE) is injecting dermal cells. The presence of dermal cells was top of the differential diagnosis for the signs in these post-Fort Dodge vaccinated horses.
It was possible that the surface antigens on the parasites present in the vaccine caused the signs. This scenario was added as number 2 to the differential diagnoses list for post-Fort Dodge vaccination neuritis.
What would happen if we vaccinated horses with cell free recombinant S. neurona SAG 1 (rSAG1)? First, do we get any immune response? We vaccinated 20 S. neurona-naive horses twice with 50 micrograms of rSAG1. We gave the shots, two weeks apart. Twenty control horses were sham vaccinated. Of course, this was after satisfying USDA we made a vaccine, validated the production, made the batches required, and filed the paperwork for the USDA approval. If this sounds like a safety study preparing for an "EPM" vaccine, it was.
There were no safety issues in the normal horses. Depression, sore necks, fever, swelling at the injection site were all absent...all systems go! We didn't see the clinical signs observed in the Fort Dodge vaccinated horses. There was a good immune response in the rSAG1 vaccinated horses. By day 35 the vaccinated horses seroconverted against rSAG1.
The next step was a horse infection challenge study in SAG1-vaccinated horses to determine if the vaccine would protect against EPM. You can read the published study Evidence that antibodies against recombinant SnSAG1 of Sarcoystis neurona merozoites are involved in infection and immunity in equine protozoal myeloencephalitis. Alas, the vaccine proved too expensive to produce and one would need to develop vaccines for rSAG5 and rSAG6. Our partners saw the light and went back to developing products for cows.
But in retrospect, what other changes could we measure in rSAG1 vaccinated horses that were not visible clinically? A few years after the vaccine work we developed the MP2/MPP ELISA, we wanted to understand the role of polyneuritis in equine diseases. Recovering the safety study samples from deep freeze we tested for the presence of antibodies against myelin protein 2. The assays showed that the rSAG1 vaccinated horses didn't produce antibody against MPP, however horses did produce anti-MP2 antibodies by day 35!
These data indicate sub-clinical polyneuritis in response to rSAG1 vaccination! We know from the literature that antigens that induce EAE are dose dependent. Our vaccine dose was enough to stimulate inflammation on peripheral nerves, but not enough to produce clincal signs in the vaccinated horses. These data support that SAG1 antigen found on S. neurona is associated with sub-clinical polyneuritis. The Fort Dodge vaccinated horses had been vaccinated with SAG1 antigen AND equine dermal cells, enough polyneuritis-causing antigens to tip the scales to clinical signs in the horses. The Fort Dodge vaccine was removed from the market after conditional approval and numerous adverse events.
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