January 16, 2010 – PZP Administration, part 1: Adjuvants

Now that we’ve gone through the way PZP works, as well as how it is made and distributed, I think we should start to talk about how it is actually administered to wild horses.

Recall that PZP works by influencing an immune response in a mare. This ends up causing the mare’s antibodies to bind to her own eggs, and this can prevent fertilization from occurring. This is possible due to the similar structure shared by the zona pellucida of pigs and horses. As such, when a mare is treated with PZP, her immune system is not totally convinced that the PZP is anything to worry about. Because of this, PZP must be prepared into a vaccine before it is administered. This is done by combining the PZP with a substance called an adjuvant.

I will describe how I think of the PZP vaccine to help illustrate what adjuvants do. If only PZP was injected into a mare, her immune system would come and take a look at what this foreign substance was. However, because it’s similar to things already in the mare, it may only produce a weak immune response; or it may do nothing at all. Remember, without a significant immune response, there will be no prevention of fertilization. This is where adjuvants come in. If PZP with an adjuvant is injected into a mare, then the immune system will again come to check things out. This time, though, the adjuvant is acting like a big, red flag taunting the immune system and making it think that it really should do something significant against the PZP. Thus, the adjuvant is almost tricking the immune system into working against a rather insignificant threat. This isn’t an exclusive use of adjuvants; they make a lot of vaccines work well. However, the type of adjuvant used with PZP is not necessarily the type used in the vaccines we may be more familiar with.

The one year dose of PZP is prepared with two different adjuvants. One is used when a mare receives her first treatment (the primer). The other is used in subsequent treatments (boosters).

For now, let’s focus on the adjuvant used in the primer. It is very important that the primer work right as it determines how well subsequent treatments work. From 1987 to 2005, a substance called Freund’s Complete Adjuvant (FCA) was used for this. FCA consists of an oil mixed with the dead and dried up cell walls of a bacteria called Mycobacterium tuberculosis. FCA isn’t used anymore for a couple reasons. First, M. tuberculosis causes tuberculosis. While the remains of the bacteria in FCA cannot cause tuberculosis, they can possibly cause false positives in the results of tuberculosis tests. That is, it is possible that tests would show that something has tuberculosis even though it really does not.  (Interestingly, there isn’t a reliable way to test horses for tuberculosis.) Second, there was some concern over FCA causing abscesses. FCA can cause abscesses to form less than 1% of the time. (We will be going more into the abscess issue in an upcoming post.) Because of these minor concerns, research was done on a different adjuvant known as Freund’s Modified Adjuvant (FMA) (Lyda, R., Hall, R., and Kirkpatrick, J.F. 2005). FMA is similar to FCA, except it has the dead and dried up cell walls of a different species of bacteria called Mycobacterium butyricum. Unlike M. tuberculosis, M. butyricum has not been found to cause any type of illness. It really has only been found in association with rancid butter. (Remember, though, the bacteria in the adjuvant cannot do anything; it is just the cell walls of it.) The study done on FMA found that it was equally as effective as FCA. Because of the benefits it has over FCA, FMA is what is used today.

Thus, the first treatment a mare receives contains a substance that is made to really get the attention of the immune system. This influences the immune system to act against the PZP. This isn’t quite enough though, and so a second treatment is given soon after the primer. Boosters are used in these subsequent treatments. Every treatment a mare receives after her primer is a booster. Like the booster vaccines given to humans keep up immunity to pathogens, the PZP boosters continue to bolster the mare’s immune system against fertilization. Still though, PZP is reversible. This is an important aspect of PZP that we’ll come back to later. Boosters use a different adjuvant called Freund’s Incomplete Adjuvant (FIA). FIA is simply an oil without any bacterial remains. This doesn’t send quite the same message to the immune system that FMA does. Still, though, it reminds the immune system of the first treatment enough to respond to the PZP in it. (Also, it should be noted that PZP pellets, which essentially act like time-release boosters, have an adjuvant made from a plant-based substance called a saponin.)

When PZP is mixed with an adjuvant, it creates an emulsion. This makes sense, of course, given that it is essentially a mixture of water (which the PZP is in) and oil. A good emulsion also helps in influencing an immune response. It is just another way used to get the attention of the immune system so that a proper response can occur. Thus, when the PZP vaccine is properly prepared, it looks like a thick foamy substance.  There are different ways that the vaccine can be injected into the mare. These different delivery methods will be the topic of my next post.

References

Lyda, R., Hall, R., and Kirkpatrick, J.F., 2005, A comparison of Freund’s Complete and Freund’s Modified adjuvants used with a contraceptive vaccine in wild horses: Journal of Zoo and Wildlife Medicine, v. 36, p. 610-616

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Published in: on January 16, 2010 at 6:08 pm  Comments (4)  

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4 CommentsLeave a comment

  1. Matt,

    Thanks so much for explaining all of this. Several of us met with the USGS researchers in Ft. Collins and they had explained their research, but I still didn’t totally comprehend the purpose of the addition of the adjuvant and what it does. Now I do!! Thanks for putting this in the vernacular so even an English major understands! The researchers actually were very enlightening with the findings of their studies and will be interested to see the ongoing results.
    Keep up the great work!

    • Linda,
      I’m happy to know this post helped. It’s great you got to attend a meeting with USGS researchers. They’ve done a lot of great research on Western herds that I’ll definitely be bringing up in some of these upcoming posts. Thanks for your support!
      Matt

  2. You’ve probably posted this somewhere, but I missed it. Do you know the efficacy rate of the PZP treated Pryor horses? I wrote down 66% but I’m not sure that’s correct, as I know it’s been 90% in some herds.

    • Linda,
      A post very soon will go into some of the research on efficacy. In the Pryors, it was over 90%; but I don’t have the exact figure on hand (I am out of town tonight). I will definitely have it in the efficacy post, though. It was tricky in the Pryors as some of the darting was done when mares were pregnant already; I understand that this was from litigation that delayed darting.
      Thanks!
      Matt


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