In February of this year we saw the launch of the first human trial for a new vaccine for Visceral Leishmaniasis.
The new trial was launched by the Infectious Disease Research Institute (IDRI) in Washington, USA with the plan to hold a further Phase 1 trial in India. The Bill & Melinda Gates Foundation is funding the Phase 1 clinical trials, as part of the recently announced worldwide partnership with the WHO and 13 pharmaceutical companies to control or eliminate 10 neglected tropical diseases.
This new development on a Leishmania vaccine can be added to a fast-expanding list of so-called “anti-poverty” vaccines; the famed RTS,S malaria vaccine that last year proved to be effective (albeit not to levels some would deem completely effective), rabies, hookworm, Schistosomiasis, and a dengue vaccine to be seen before 2015.
Visceral Leishmaniasis represents one form of a disease seen across much of the old and new world — across 88 countries — and is one of the most common parasitic infections behind malaria. In India, they refer to it after the Hindi word that means black fever — kala-azar. The black fever that haunts those infected and whose skin becomes dark and gray. Where ever it infects, kala-azar is the most deadly form of leishmaniasis.
For the sake of brevity, the history of a Leishmaniasis vaccine dates back to the 1940s with “leishmanization” as it was known. The deliberate inoculation of infective and virulent Leishmania from the “exudate” of a lesion on the skin. Crude, unreproducible and wholly unsafe, the method of leishmanization gave way to first generation vaccines, consisting of killed or live attenuated parasites.
Second generation vaccines came much later; when we were able to genetically modify the leishmania species themselves or use bacteria or viruses as surrogates carrying leishmania genes.
Some methods rely on the identification, thanks to genome sequencing, of proteins on the parasite’s surface that can be used to elicit an immunological response. And most importantly, a protein that is expressed in more than one life cycle stage of the parasite.
More recently, the ability to manipulate the Leishmania genome to create genetically modiﬁed parasites by introducing or eliminating genes meant the potential of using live attenuated parasite vaccine. And represents a powerful alternative for developing a new generation vaccine against leishmaniasis.
The prospect of DNA vaccines came only when it was discovered that directly injecting relatively small circles of DNA that encode foreign proteins could lead to a specific immune response. Only then was a new perspective of vaccine formation imagined. One that had no need for the invading parasite itself, and one driven by our advances in molecular biology and biotechnology.
Elliciting an immune response to leishmania is something easier said than done. Many early vaccines that showed promise lacked the ability to ellicit the exact kind of immune response. This is a fact made even more complicated by the fact that leishmania as aparasite lives within immune system cells (macrophages). Leishmania survive within host cells, hiding and inhibiting the cell’s interior defenses.
The IDRI vaccine, known as LEISH–F3 + GLA-SE, is a highly purified, recombinant vaccine. It incorporates two fused Leishmania parasite proteins and a powerful adjuvant to stimulate an immune response against the parasite.
With a slow realisation that the geographical range for leishmaniasis is expanding, a vaccine could not come at a better time. Spurred on by global warming, mass migration and rapid urbanization, cases are being reported in previously unaffected areas.
Vaccines are seen as the silver bullet — the game changer. Sophisticated pieces of science that are so simple in their function. For all we know about the way our own immune system works, there still lies large blind spots and gaps in our knowledge. The delicate balance and complexity hidden within the immune system is only made evident when diseases and germs find a way to avoid and exploit it. The possibility of a kala-azar vaccine is made even more sweeter by the simple fact that the leishmaniases are unique among parasitic diseases because a single vaccine could have the potential to protect against other leishmania diseases.
Image — source.
Originally appearing at endtheneglect.org
Dunning, N. (2009). Leishmania vaccines: from leishmanization to the era of DNA technology Bioscience Horizons, 2 (1), 73-82 DOI: 10.1093/biohorizons/hzp004
Chakravarty, J., Kumar, S., Trivedi, S., Rai, V., Singh, A., Ashman, J., Laughlin, E., Coler, R., Kahn, S., Beckmann, A., Cowgill, K., Reed, S., Sundar, S., & Piazza, F. (2011). A clinical trial to evaluate the safety and immunogenicity of the LEISH-F1+MPL-SE vaccine for use in the prevention of visceral leishmaniasis Vaccine, 29 (19), 3531-3537 DOI: 10.1016/j.vaccine.2011.02.096
Nagill, R., & Kaur, S. (2011). Vaccine candidates for leishmaniasis: A review International Immunopharmacology, 11 (10), 1464-1488 DOI: 10.1016/j.intimp.2011.05.008