Friday, May 25, 2012

Sleeping Sickness Vaccine Strategy

Sleeping sickness is caused by a trypanosome (not a bacterium so ordinary antibiotics don't work). It kills people, is principally reproduces in cattle. Long ago, I had a thought about anti sleeping sickness vaccine strategy. Now I am thinking of trying the very experimental approach in cattle -- experiments with cattle are not regulated as tightly as experiments with humans must be.

A key feature of the sleeping sickness trypanosome is that the major surface protein switches among roughly 10 types. This is a trick to evade the host's immune system. The trypanosome must have other surface proteins which can't be changed to serve as ion pores etc. I think a vaccine made of killed trypanosomes is not effective, because the immune response is directed at the changing major antigen. I also guess that the other unchanging proteins induce antibodies.

The plan would be to immunise with whole trypanosomes, clone the resulting IgG genes in an M13 phage display library and screen for antibodies which bind to trypanosomes with different major coat proteins. Then use those antibodies to screen for (or select even) the genes which make the constant proteins (or constant epitopes on the major coat protein). Then make those target proteins highly antigenic.

Huh ? how ? with bovine anti-CD40. Does it exist ? Ask the google. Yes it does. Also there is a mouse model of the bovine immune system (using SCID mice). It is possible to begin to evaluate vaccines designed to protect cattle from sleeping sickness without letting cattle into the lab (bull in a china shop indeed).

Anti CD40 as an adjuvant (means something you add to a vaccine to make it work better) is a topic of great interest and slow progress, because human vaccines are to be given to healthy people so research is especially ultra tightly regulated (as it must be). So others have thought already that the thing to do is to work with antibodies to other animals' CD40. It's happening. I think it is very promising. But what do I know ?

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