A new vaccine against malaria using parasites from irradiated mosquitoes has just passed the first phase of clinical tests with 100% success, surpassing large difficulties in production and improving greatly on any previous attempts. If further trials confirm this result and obstacles to distribution and application are removed, an end to malaria may be in sight.
At the start of August, Science magazine reported on the impressive results of PfSPZ in its first safety trial. This vaccine was developed by Stephen Hoffman's team in Sanaria, a company based in Rockville, Maryland, using parasites from irradiated mosquitoes. The six subjects given five doses intravenously were 100% protected from later bites by infected mosquitoes, whereas five of six unvaccinated controls developed malaria, as did three of nine people given only four doses of the vaccine . Previous vaccines had never come close to this level of efficacy.
The next phase is the implementation of larger trials in regions where malaria is rampant, which will test for protection against different strains and on different age groups. One is already set to start in the Ifacara Institue in Tanzania. Hoffman hopes to have a vaccine licensed within four years.
If that goal is achieved, the benefits to developing countries will be enormous. Every year, malaria kills between one and three million people, and infects as many as half a billion people . The economy slows down and a huge burden is placed on the health system.
An effective, widely distributed vaccine would highly reduce the incidence of malaria and therefore make a crucial contribution to these countries' development, as acknowledged by the World Health Organization (WHO), which set as a target the creation of a vaccine with 80% efficacy by 2025 . Is the PfSPZ going to be the vaccine to achieve this?
Results from the 1970's which showed that immunization with over 1000 bites by irradiated sporozoites confers about 90% protection against infection, lasting for 10 months . Hoffman decided to try to create a vaccine of equivalent effect.
This led him to using the whole Plasmodium falsiparum (Pf) - the parasite which, out of the four strands that cause malaria, accounts for almost all the fatal cases - in the sporozoite (SPZ) stage of its life cycle. This approach was radically different from the mainstream line of employing just a handful of proteins from the parasite. Initially, many researchers were sceptical of the possibility of mass-producing sporozoites (between ten and a hundred thousand per vaccine) within the required health and safety standards.
Against the odds, Hoffman's team managed to construct a successful production process. The researchers raised mosquitoes in industrial quantities, fed them with infected blood, and irradiated them to weaken the parasites, so that they can infect but cannot cause the disease. After that, the parasites were harvested from the mosquitoes' salivary glands, purified and cryopreserved to obtain the vaccine.
Despite the initial success, optimism must for now remain cautious. First of all, unlike most widely used vaccines, which are given orally or by injection just under the skin, the PfSPZ is intravenous. This makes it harder to apply, particularly to children. As 70% of malaria deaths are of children under five, this is a serious issue.
Under-the-skin vaccine trials have not been successful: in 2011, only two out of eighty participants were immunised . Hoffman claims that the small volume of the vaccine (0.5 millilitres) and the tiny syringe required will make it widely applicable, especially taking into account that the company is looking into improving the intravenous delivery system; but other researchers believe that it won't be possible to use on children.
Secondly, the vaccine needs to be kept frozen in vapour nitrogen phase, which is an obstacle to distribution. However, it should be able to piggyback on veterinary infrastructure, and to be transported with veterinary medicine and semen for insemination of livestock.
Though it is still hard to predict whether this vaccine will be successful, it is undeniable that it represents a big step in malaria research, and that it gives new reasons for optimism about reducing the incidence of the disease.
 Seder, R. A. et al. Science http://dx.doi.org/10.1126/science.1241800 (2013).
 Hoffman, S. L. et al. J. Infect. Dis. 185, 1155-1164 (2002).
 Epstein, J. E. et al. Science 334, 475-480 (2011).
Butler, D. Nature News http://www.nature.com/news/zapped-malaria-parasite-raises-vaccine-hopes-1.13536 (2013)
Image from http://www.againstmalaria.com
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