Using a parasite as a vaccine…

A group of researchers (see reference below) have been looking at a very interesting new method of vaccine delivery: using trypanosomes.

T. (megatrypanum) theileri  is found infecting cattle worldwide.  It is transmitted by flies and gains entry to the animal either through broken skin or via mucous membranes and once the animal is infected it tends to carry low numbers (~100 organisms/ml) of trypanosomes for the rest of its life. Although there is some evidence suggesting that infection with this organism has the potential to cause a drop in milk yield in some cattle the authors state that the “ubiquity of infection with this organism in cattle herds suggests that it has no significant impact on health or productivity in healthy animals”. 

Because of this apparent lack of pathogenicity and because the parasites persist for such a long time in the host the researchers thought they could potentially use the trypanosome to deliver antigens (molecules that will trigger an immune response) from other, more pathogenic organisms to the cattle, so effectively using it like a vaccine.

The researchers tested this by genetically modifying the trypanosome to produce Bd37 – an antigen from Babesia divergens (which causes a disease called “redwater fever” in cattle).  They engineered 3 different groups of trypanosomes.  The first expressed the Bd37 within themselves (intracellularly), the second expressed the Bd37 on their surface (extracellularly) and the third actively pumped out the Bd37 (secretory).  They then infected cattle with the trypanosomes.  After inoculation they took blood samples at regular timepoints to look for any antibody response.

All of the cattle became infected with the trypanosomes and they stayed infected for the entirety of the 12 week period of the trial.  The number of cattle that started to produce antibodies against Bd37 after infection were:

Intracellular group: 4/6

Extracellular group: 3/6

Secretory group: 5/5

The researchers also showed that those in the secretory group had significantly higher antibody levels than the other two groups.  The antibody levels of all animals that produced them continued to increase for 60 days and remained high for at least another 24 days (which was as long as they were measured for).

Finally the researchers compared the antibody levels achieved with the trypanosome method of delivery with a traditional vaccine delivery and they found that the antibody levels were “equivalent”.  (So this trypanosome delivery method is effectively providing as much protection as the traditional vaccine.)

If this method does not produce better antibody production than a standard vaccine why would you go to the bother of engineering these trypanosomes?  Well the researchers say that this method of delivery has several advantages:

1. As trypanosomes can cross mucous membranes there is the possibility for vaccine delivery
2. As the trypanosomes infect the host for a very long time, potentially for the rest of its life, they could potentially stimulate an immune response against a target antigen for this length of time, so providing immunity for a longer period than a traditional vaccine

Another advantage is that T. theileri is already non-disease causing in cattle.  Some vaccine delivery systems use attenuated bacteria such as Salmonella but these bacteria have the potential to revert to being disease-causing.  As T. theileri doesn’t cause disease this isn’t something the researchers need to worry about.

So all of this research is very promising and suggests that with more research trypanosomes could be used in the future to protect cattle from disease.

But I’ve tagged this as a ‘zoonosis’ post and so far only talked about cattle diseases.  What relevance does this have to human health? 

Blood smear from patient with African trypanosomiasis. Image taken by the US Centre for Disease Control and Prevention.

Human African Trypanosomiasis, also known as sleeping sickness is a fatal disease that occurs in sub-Saharan Africa.  It is caused by the trypanosomes Trypanosoma brucei rhodesiense and Trypanosoma brucei gambiense.  These trypanosomes are spread from person to person by the tsetse fly (it bites infected Person A, takes a blood meal which contains trypanosomes, flies off and then bites uninfected Person B, infecting them as it does so).  The main reservoir for T. brucei gambiense is the human population however cattle are an extremely important reservoir for T. brucei rhodesiense.

T. brucei rhodesiense (as you can tell by the name) is closely related to another trypanosome that infects cattle T. brucei brucei.  This trypanosome only infects cattle – it can’t infect humans because a substance called ApoL1 found in human serum kills it.

The researchers speculate (and it is currently only speculation) that if T. theileri was used to deliver a modified form of ApoL1 that killed T. brucei rhodesiense  this vaccine system could be used to dramatically reduce the cattle reservoir of this dangerous parasite.  There is a HUGE amount of work that needs to be done before this can even be trialled but it has the potential to make a great impact on human health. 

Watch this space!

 

Images

The trypanosome image came from the paper (see below).

The blood smear image is available on Wikimedia Commons here

 

Further Reading

WHO information on Human African Trypanosomiasis

Mott, G., Wilson, R., Fernando, A., Robinson, A., MacGregor, P., Kennedy, D., Schaap, D., Matthews, J., & Matthews, K. (2011). Targeting Cattle-Borne Zoonoses and Cattle Pathogens Using a Novel Trypanosomatid-Based Delivery System PLoS Pathogens, 7 (10) DOI: 10.1371/journal.ppat.1002340