Research Roundup: a rapid diagnostic for Ebola and fighting mosquito-borne diseases with soap and coconuts

Last Wednesday, researchers from the Washington University School of Medicine, the University of São Paulo, and the Chinese Academy of Sciences offered new insights into the impact of the Zika virus on fetal brain development in mice, publishing their findings in Cell, Nature, and Cell Stem Cell, respectively. The first two studies sought to successfully infect pregnant mice with Zika—a feat in itself as mice don’t often fall ill after infection with the virus. Consequently, the team at Washington University used a genetically modified mouse with a weakened immune system as well as a mouse whose immune system was weakened by an antibody, while researchers at the University of São Paulo used a particularly high dose. The team at Washington University detected placental insufficiency in the infected mice—which limits blood flow to the fetus—and the team at University of São Paulo reported intrauterine growth restriction, a condition restricting the growth of the fetus. When the virus reached the fetal brains, both teams witnessed a thinning of brain tissue and cell death. The concentration of the virus in the brain was limited, which inhibited further research on how Zika behaves once in the brain. The team at the Chinese Academy of Sciences, however, injected the virus directly into the brains of fetal mice, and they determined that the virus targets neural progenitor cells and causes the fetal brain to shrink. Silk has been used in developing heat-stable vaccines and drugs, and now, researchers at Tufts University have demonstrated that silk can be used to maintain blood samples in low-resource settings. Blood-based diagnostics are only effective if certain proteins, which indicate either the presence of a pathogen or the immune system’s response to it, are preserved, however, heat and humidity can directly damage the proteins or cause enzymes in the blood to attack the proteins. Labs prefer that blood samples are refrigerated, although they can also be dried on special filter paper that can withstand heat but which often doesn’t hold enough blood for analysis. The team at Tufts created a silk-based powder and solution, combined it with blood samples, and allowed it to dry. The samples were then stored at high temperatures (72 to 113ºF) and remained viable for 84 days. GHTC member the International Vaccine Institute (IVI) announced last week that a single dose of the oral cholera vaccine Shanchol, currently administered in two-dose regimens, provides protection against the disease. The two-dose regimen provides 65 percent protection against cholera for at least five years, while the single dose demonstrated 40 percent protection against the disease for at least six months. While the two-dose regimen is preferred, the single dose could be appropriate for epidemics or in settings where the two-dose vaccine schedule is impractical. The study enrolled 204,700 individuals residing in the urban slums of Mirpur in Dhaka, Bangladesh, where cholera is endemic. In addition to reducing cases by 40 percent, the vaccine resulted in a 63 percent decrease in cases of severely dehydrating cholera.

There is a safe, affordable, single-dose vaccine that protects against yellow fever for 99 percent of those vaccinated, yet a recent outbreak of the disease has resulted in nearly 2,000 cases and killed 258 in Angola. Yellow fever is endemic in 44 countries, including Angola, and the global demand for the vaccine surpasses availability by 42 percent. Additionally, the cost of the vaccine has increased 30 percent annually. The vaccine is currently produced by four manufacturers, and its production is complicated, requiring embryos in chicken eggs. A vaccine with an inactivated version of the virus, which would be much easier to manufacture, has successfully completed phase 1 clinical trials, however, it has not yet been commercialized. As the World Health Organization is leading negotiations to divert yellow fever vaccines from routine immunization programs to Angola, the existing vaccine could also be delivered in smaller quantities to more people: just one-fifth of the standard dose has proven to be effective against the virus. A team of American and German scientists have demonstrated that an injection with potent anti-HIV antibodies can protect against the virus in monkeys for nearly six months. The researchers used four different antibodies that have proven to be effective against various HIV strains and administered one type each to four different groups of monkeys. The monkeys were then exposed to the virus on a weekly basis. On average, the monkeys were protected for 12 to 14 weeks, although some were protected for up to 23 weeks. Previous studies have shown that antibodies can provide short-term protection against HIV in monkeys, however, in most studies, the monkeys were exposed to the virus in one high-dose shot. In reality, most infections in humans develop gradually as a result of repeated, low-dose exposures, and thus, this study sought to emulate standard human transmission. Currently, the first-ever clinical trial of a single antibody is being tested in individuals at high-risk for HIV infection, however, it’s expected that a cocktail of these potent antibodies would be even more effective at preventing infection.  New research out of Florida Gulf Coast University indicates that previous infection with dengue virus could exacerbate symptoms from the Zika virus. This phenomenon—antibody-dependent enhancement, in which the presence of protective antibodies against one disease increases vulnerability to another—has been reported among different strains of dengue virus. The team at Florida Gulf Coast University confirmed that in cell cultures, the presence of antibodies against dengue intensified Zika infection, however the research also suggests that a single vaccine candidate could be effective against both diseases. These findings, coupled with the shared Aedes aegypti mosquito vector, indicate that the spread of Zika in dengue-endemic regions could be more virulent than expected.