Newsworthy: Vaccine linked to “bleeding calf syndrome”

When I first started working in an actual clinic, I was blown away with the education I received in vaccine administration. Before at the shelter my instruction included solely how to administer them and not to be bitten while doing so. Spending a minute to educate clients on vaccine reactions, the steps we took to prevent them from happening, and the importance of the proper scheduling of a series were all new to me, and considering how seriously we took all these things, it vastly contrasted with my training at the shelter. How vaccines work has always been interesting to me, and the immunology involved isn’t terribly complicated on the surface. Even if the mechanisms escape me, I can still visualize the flowchart (something I wish I could consistently do with G-proteins, a crucial topic but one I constantly have to review).

Image from Veterinary Laboratories Agency

Anyway, the point is I was really interested in this article. Bleeding calf syndrome is technically called bovine neonatal pancytopenia (BNP), but is probably still a frightening thing to see. It actually only emerged in 2007. The characteristic bleeding is caused by thrombocytopenia after the calf’s bone marrow becomes compromised. The lack of platelets causes the appearance of bleeding through the skin the name refers to. A group of doctors in Germany were able to determine the etiology of the condition (which has a calf mortality rate of 90%). Based on another study, they knew that the colostrum given to affected calves could also induce the symptoms in other unrelated calves, and after not finding evidence from pathogenic or genetic causes looked at an “immune mediated process” (Deutskens, 2011).

What they found was that there was a correlation between cows vaccinated for Bovine Viral Diarrhea Virus (BVDV) and calves suffering from BNP. After a lot of spectroscopy and protein identification, they found that the vaccine actually was the cause. What the issue was, is that the BVDV vaccine is made using kidney cells from cows, instead of another species (for example many human vaccines are cultured in pig cells). Here’s how that works: there is a specific protein “map” coating all nucleated cells that the immune system uses to identify which team they play for. Anything with a different protein coat is assumed to be foreign, and is attacked. This is the major reason why donated organs are rejected, because the donor has a slightly different “map” than you and your immune system assumes it’s trying to hurt you. With the vaccine grown in bovine cells, remnants or copies of this Major Histocompatability Complex (MHC, the “map”) are introduced to the mother, who has an immune response to them.

This is where it gets interesting, the antibodies the mother makes to attack this are called alloantibodies, and they don’t hurt the mother. They just become another antibody she reserves along with the ones that attacked the rest of the BVDV vaccine. None of her cells have that foreign “map”, so none of her cells need to worry about that extra antibody she created. However, the alloantibody gets stowed away in the colostrum along with all the others just before partuition, still ready to attack the MHC the vaccine was made with. If by coincidence the MHC of the calf is the same as the one in the vaccine cultures, then those alloantibodies given to the calf through the dam’s colostrum will attack cells within the calf, starting with blood cells and moving to the bone marrow. Making it technically not an auto-immune response, because it comes from a foreign immune system, but still a case of friendly fire. Those alloantibodies in the colostrum treat every calf cell featuring that MHC as if it’s an infection.

It should be noted that other vaccines for BVDV that are grown using non-bovine cultures do not cause these problems. This is because if the mother creates antibodies for the MHC of another species, there is no way that the calf can be affected by them. The authors of both the news article and the journal article mention that this serves as an example why same-species vaccine cultures and formation of alloantibodies should be avoided.

Check out the journal article for yourself, the introduction and discussion are well written and interesting. There’s also a similar alloantibody caused disease in humans called Neonatal Alloimmune Thrombocytopenia that’s interesting, the major difference being that the alloantibodies are introduced through the placenta instead of ingested through colostrum.

ResearchBlogging.orgDeutskens F, Lamp B, Riedel CM, Wentz E, Lochnit G, Doll K, Thiel HJ, & Rumenapf T (2011). Vaccine-induced antibodies linked to Bovine Neonatal Pancytopenia (BNP) recognize cattle Major Histocompatibility Complex class I (MHC I). Veterinary research, 42 (1) PMID: 21878124

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