A DNA Vaccine for Schistosomiasis
Alison Han

A new type of vaccine has recently been introduced, which contains simply DNA. The traditional vaccines used to immunize for measles, mumps, and polio contain live attenuated organisms, while those for polio and rabies contain killed forms. The impact of this new vaccine is great in that it can be used for a variety of illnesses. Since the introduction of the DNA vaccine, or gene vaccine, trials for immunization against HIV, cancer, malaria, influenza, and many others have quickly begun. Because this new vaccine contains no form of the organism, possible infection is not a problem and repeated immunizations are not needed. It is also advantageous over the previous vaccines in that DNA is heat stable, so that it does not necessitate refrigeration. Since DNA is relatively easy to clone, the simpler technique is more cost-efficient as well. For these reasons, this new technique is in trial for the treatment of schistosomiasis. Schistosomiasis is a parasitic disease that affects millions of people worldwide and it is most prevalent in third world countries. The reason for this is that it is transmitted via a snail intermediate, which are most often found near sources of water. While there is a chemotherapy treatment for schistosomiasis, it is expensive and not readily available. And those infected and treated are prone to re-infections. A DNA vaccine, if any at all, would be fitting for this type of environment.

So how does the vaccine work? It is made by first isolating the target molecule and cloning it. It is then inserted into a plasmid vector, resulting in a coiled piece of DNA. This can then be injected into the muscle, or using a gene gun, it can be transferred into the tissue by particle bombardment-mediated transfer. Once in the body, the DNA begins producing the desired protein. The presence of this particular protein thus stimulates a specific immune response. The point of our project was to assess the safety of DNA use. Since the vaccine technique is so new, not much is known about how it actually works. While current results look potentially positive, it is important to learn more about how it works before beginning human trials. Our first trial began with 60 mice, 30 injected into the left tibialis anterior with the plasmid vector plus the desired protein DNA, called SM25, and 30 without the SM25 as controls. The mice were injected once, twice, or three times, and than sacrificed and bled at 14, 28, or 42 days. Some of the mice were sacrificed at 1 hour, 1 day, and 2 days to determine the location of the DNA. Blood, kidneys, testes, lungs, lymph nodes, ears, spleens, left tibialis anterior and right tibialis anterior muscles were removed from these. DNA from the tissues was isolated and purified using a QiaAmp Tissue kit. PCR amplified the desired DNA and a gel was run to detect the presence of the DNA. An immunoblot was performed on the blood sera to detect presence of antibody.

PCR results showed that in the SM25 injected mice, DNA was present in the spleen, lymph nodes, kidneys, liver, lung, and ear. After one day, DNA was seen in the spleen, lymph nodes, testes, and left tibialis anterior muscle. In the non-SM25 injected mice, DNA was located in the lymph nodes, lungs, testes, and left tibialis anterior muscle. After one day, it was no longer detected. And after two days, the DNA was not seen in any of the mice. The immunoblots showed responses from two mice at day 42, one with two inoculations, the other with three.

The good news is that the DNA is seen in the lymph nodes, which is one place of immune response. One possible problematic area is the DNA in the testes. If this DNA were to be passed onto offspring, it has the possibility of being incorporated into the offspring’s DNA, which may cause genetic problems. A new trial has begun using the SM25 plus CpG specific DNA which is supposed to boost immune response, so hopefully more of the mice will respond to the PCR and immunoblot.

Since mice suffer from schistosomiasis in much the same way as humans, these trials have great possible impact in treating this disease. As we repeat and improve upon the vaccine at each trial, we are one step closer to a possible vaccine to treat schistosomiasis. So once the safety and efficacy of the vaccine can be successfully assessed, human trials may begin.

References:

1. Kalinna, Bernd H. “DNA Vaccines for parasitic infections” Immunology and Cell Biology 1997; 75: 37-375.
2. Simmonds, R.S., Shearer, M.H., Kennedy, R.C. “DNA Vaccines From Principle to Practice” Parasitology Today 1997; 13: 328-331.
3. Taubes, Gary “Salvation in a Snippet of DNA?” Science 1997; 278: 1711-1714.