Tuesday, December 11, 2007

Malaria Vaccines - Sanaria Goes Back to Basics....Way Back

The last twenty years or so have seen various attempts at making an effective anti-malaria vaccine using the latest and greatest scientific techniques. Subunit vaccines, DNA vaccines, recombinent vaccines using viruses as vectors, vaccines targeting pre-erythrocytic stages, erythrocytic stages, even the parasite stages that are found in the mosquito vector.

It now appears, according to an article in today's NYT Science Times, that scientists at a company called Sanaria, are attempting to use techniques that go way back to the 50's and 60's for developing an anti-malaria vaccine. The technique involves obtaining a stage of the malaria parasite called a sporozoite from malaria-infected mosquito salivary glands. Obtaining mosquito salivary glands is done by gently separating the head of the mosquito from the thorax. Tedious work I can assure you, since I personally spent many hours doing so.

To really appreciate the complexity of malaria and producing an anti-malaria vaccine you really need to understand the malaria life cycle.

Different forms (stages) of the malaria parasite are found in the mosquito (very specific mosquito species and only females), in the liver and in red blood cells. Malaria infection begins with the bite of an infected mosquito. The mosquito injects a stage of the parasite called a sporoszoite into the blood vessel of a human host. It is the sporozoite that one hopes the immune system will target and destroy. Unfortunately, within about 30 minutes or so, the sporozoite penetrates the cells of the liver (hepatocytes). This is unfortunate for a couple of reasons. First, the sporozoite is no longer free in the bloodstream available to attack from antibodies and phagocytic cells. Second, once penetrating the hepatocytes, the sporozoite changes....it is no longer recognized by the immune system as a sporozoite. 100% of the malaria sporozoites must be destroyed by the immune system prior to the sporozoite penetrating the liver. A single surviving sporozoite can result in malaria.

It was shown 40 years (or more) ago that if you irradiate malaria sporozoites with just the right amount of gamma radiation, the sporozoites are still alive but can no longer penetrate the liver. This allows the sporozoites to remain in the blood stream thus stimulating the immune system to develop high levels of specific anti-sporozoite antibodies. Small experimental anti-sporozoite vaccine trials have been done on humans. In the late 40's prisoners at Stateville prison near Joliet, IL were used as experimental subjects. The results of these trials were not that impressive.

So, the multi-million dollar company Sanaria has gone back to the days of yore to find the illusive malaria vaccine. This involves raising roomfulls of mosquitoes which are infected with the most dangerous species of human malaria - Plasmodium falciparum. You do not want these mosquitoes to escape. A team of technicians must dissect infected salivary glands from tens of thousands of mosquitoes - a really, really boring job. The malaria sporozoites must be separated from the mosquito salivary gland tissue. This is really important. When mice that received a prior injection of ground up infected mosquito salivary glands were given a second injection of the same material...the majority of the mice would die within five minutes due to anaphylactic shock. The purified sporozoites must then be irradiated and frozen (cryopreserved). A crude vaccine prepared pretty much the way Pasteur made vaccines well over 100 years ago.

Will this work? And by work, I mean rid the world of malaria. In my humble opinion...no.

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