WASHINGTON — When approached with the concept for producing the PfSPZ malaria vaccine, Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, thought it technically unfeasible. Actually, he called it “crazy.” His skepticism was overcome in a
WASHINGTON — When approached with the concept for producing the PfSPZ malaria vaccine, Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, thought it technically unfeasible. Actually, he called it “crazy.” His skepticism was overcome in a stunning feat of biomedical engineering, offering the prospect of life and health for millions.
Malaria researcher Stephen Hoffman raised hundreds of thousands of mosquitoes in a sterile environment and fed them infected blood, producing malaria sporozoites (an early stage in the life cycle of the plasmodium parasite) in their bodies. The mosquitoes were placed in containers and irradiated, which weakens the sporozoite without killing the host. Then dozens of technicians working in cubicles performed micro dissections — harvesting the parasites from the salivary glands of the mosquitos, one insect at a time. The sporozoites were then purified and cryogenically stored.
This unlikely method produced enough vaccine for a 40-person trial at the National Institutes of Health in Bethesda, Md. Of those given five injections of the highest dose of the weakened parasite, 100 percent were protected against the disease.
Developing a vaccine against a parasite is inherently more difficult than against a virus. A virus exists in one form and has a simple replication cycle; a parasite develops in various stages, all of which can exist in the body at once. The PfSPZ vaccine solves this problem by eliminating the malaria parasite at the beginning of its life cycle. When injected by the mosquito, sporozoites travel through the blood stream to the liver, where they start replicating. The new vaccine produces a T-cell response that works within the liver, essentially killing the parasite in its nursery. “The time in the cycle,” Fauci told me, “is critical to prevent infection.”
The study at NIH was small. Before the end of this year, there will be larger trials in Tanzania and Mali, supported by the Tanzanian government, a Swiss institute and the NIH. Malariologists will test the durability of the vaccine’s protection and its effectiveness against variations of the parasite in the wild (there are many strains of plasmodium falciparum that cause malaria in humans).
If the vaccine works as promised, it would be an extraordinary scientific milestone: the first highly effective vaccine against a parasite. And this particular parasite has been living in human hosts — and killing them — since humans evolved. About 650,000 people die of malaria each year, mainly children under 5. A vaccine that prevents infection — rather than treatments that modify the severity of the disease — is important to malaria eradication. Even people with a low level of parasites and no symptoms can transmit the disease, through mosquitoes, to others.
There are serious obstacles in moving this type of vaccination to the necessary scale (beyond, say, to tourists and soldiers). The marvel of the production process — involving individual mosquito surgeries — is itself a constraint. It would need to be somehow automated. It is a problem that the vaccine is delivered intravenously — relatively untrained health workers can’t be expected to find and hit the veins of children (which any medical intern will tell you are maddeningly small). A better delivery technology is required. A five-dose regimen is difficult to implement. And like other temperature-sensitive vaccines, a continuous cold chain is essential.
Yet if public health officials were content to whine about obstacles, mass treatment for AIDS would never have been undertaken. On a malaria vaccine, Fauci sees a number of problems “we haven’t cracked yet.” But, he continues, “Once you have proven the concept, everything else is engineering. The stakes are so high. A baby dies every 60 seconds from malaria. I can’t imagine that some engineering genius can’t figure these things out. Let’s go for it.”
There is, of course, one additional obstacle on the issue of malaria. A medical breakthrough on erectile dysfunction, for example, has a built-in global market of the wealthy. Malaria is found in poorer parts of the planet and helps to make those places poor. By one estimate, 58 percent of malaria deaths occur among the world’s bottom 20 percent in income — the most economically unequal suffering of any major public health crisis. In practice, this means the profile of the average malaria victim is a child in sub-Saharan Africa. Hardly the most promising market for expensive medical innovations.
So any adequate response will require a combination of public and private resources — from governments, international institutions, foundations, and innovative privates companies — along with the crazy, humane determination to go for it.
Michael Gerson’s email address is michaelgerson@washpost.com.
