June 12, 2016

Research Roundup: Schistosomiasis drug resistance, a nanotechnology vaccine platform, and adjusting doses to bolster the yellow fever vaccine supply

Senior Program Assistant

Schistosomiasis, the second most common parasitic disease, infects more than 240 million people each year, and can result in liver failure, bladder cancer, and even death. Schistosomiasis is treated using the antiparasitic drug Praziquantel, however, resistance to the drug has been reported in Kenya and Uganda. Despite its efficacy, the mechanism of action of Praziquantel remains a mystery; scientists don’t understand how it combats schistosomiasis. By comparing the genomes of parasites that are sensitive and resistant to the drug, researchers at the Texas Biomedical Research Institute and the University of Texas have identified genes that are associated with resistance, and have received a US$3.5 million grant from the US National Institutes of Health to further examine the individual genes and mutations that confer resistance. The team will collect parasite eggs from patients in Kenya and Uganda before and after treatment with Praziquantel; the eggs from patients who are cured and those that remain infected will be classified as sensitive and resistant to the drug, respectively. They will then sequence the parasites’ genomes, honing in on the genes and mutations linked to resistance, with the goal of better understanding how resistance develops. This information is critical to developing drugs that are effective against Praziquantel-resistance parasites and diagnostics that can detect resistance.

5 month old infant receiving an oral polio vaccine (Photo: PATH/Gabe Bienczycki)

Researchers at the All India Institute of Medical Sciences (AIIMS) have completed successful animal trials of an oral vaccine against hepatitis B using a nanotechnology platform that could be adapted for other viruses. Oral vaccines are challenging to develop, as the key components are often degraded in the stomach before they can be absorbed through the intestines. However, they offer significant advantages: they don’t require needles and consequently there’s no risk of blood contamination, many don’t need to be kept cold, and they often spread more thoroughly throughout the immune system. The existing vaccine against hepatitis B is injectable and requires three to four doses, whereas the vaccine under development at AIIMS could be potent enough to require just a single dose. The team used nanoparticles to house the antigen—the part of the vaccine that triggers an immune response—and covered the nanoparticles in a protective surface that can survive the stomach. The vaccine will next be tested in human clinical trials, which the team hopes to complete by 2021.

The World Health Organization (WHO) is proposing new guidelines for yellow fever vaccination in emergencies, as alarming outbreaks in Angola, Uganda, and Peru intensify due to a limited global supply. Clinical trials suggest that the vaccine is effective at much smaller doses, and the WHO is expected to recommend that member states use just one fifth of the standard dose. However, the studies were conducted exclusively in adults, raising concerns that the fractional dose might not be enough to protect children. It’s also unclear if the smaller dose would provide lifelong immunity, and the WHO’s proposal will likely recommend a booster to be administered at a later time. Once complete, the proposal will be submitted to the WHO’s Strategic Advisory Group of Experts on Immunization for review, and if approved, will be implemented if the outbreak reaches emergency levels.