A biologist releases genetically modified Aedes Egypti mosquitoes in Piracicaba, Brazil, in February 2016. The modified mosquitoes, which cannot transmit Zika, compete with wild mosquitoes. Image Credit: Victor Moriyama/Getty Images
Zika virus has spread to almost 60 countries since early 2016. Almost 5000 cases have been identified in the United States, including more than 200 infections transmitted in Florida and Texas. Though the virus often causes only mild symptoms (or may not cause any symptoms at all), the link between Zika infection, microcephaly, and other developmental abnormalities has been strengthened with additional studies over the past year. However, a vaccine is still unavailable.
The scientists used a novel type of vaccine to immunize mice and monkeys, taking RNA molecules that code for viral proteins (messenger RNA, or mRNA). Because these RNA molecules would usually be quickly cleared by the body, the RNA in the Zika vaccine was modified by the addition of a modified nucleoside. The nucleoside is a nucleotide—the building blocks of DNA—lacking a phosphate group, which previous studies have shown helps to “hide” the mRNA from the host and allow replication. The mRNA was also packaged within lipid nanoparticles, encouraging protein expression. This vaccine therefore allows the mRNA to enter cells and induce production of the viral protein, causing a host immune response similar to that seen with a live virus vaccine. Researchers found that a single dose of the mRNA vaccine effectively protected animals against Zika virus.
Senior author Drew Weissman, of the University of Pennsylvania, relayed the advantages of this approach in a phone call with mental_floss. “The main advantages of our RNA vaccine is that only a single administration is needed. For all of the DNA and inactivated vaccines, they have to immunize twice to get protection, so we get much higher levels of neutralization with a single immunization. The only other vaccine that had protection after a single immunization was the live virus adenovirus vaccine.”
Live vaccines are difficult for a number of reasons, including potential side effects, and cannot be used in pregnant women—a main risk group for Zika infections due to the virus’s effects on the developing fetus. Weissman also noted the mRNA vaccine is inexpensive to produce, which could facilitate widespread use even in resource-limited countries.
Scientists hope to start human clinical trials with the Zika mRNA vaccine in 12 to 18 months. In the interim, additional experiments are planned in order to begin studying whether this Zika vaccine could potentially lead to increased illness with a related flavivirus: dengue. Dengue infection can lead to a phenomenon called “antibody-dependent enhancement,” where antibodies make disease worse instead of protecting the host from infection. There is concern that those vaccinated for Zika could experience more severe dengue infections in areas where both viruses circulate.
To examine whether their Zika vaccine could cause this effect, Weissman says, “We’re taking two approaches. We want to look at antibody-dependent enhancement between different flaviviruses. We’re also working on a combination vaccine that includes all of the flavivirus RNAs together, and the hope there is that with a single vaccine we can immunize against Dengue, West Nile, Zika, Japanese encephalitis, or whatever flaviviruses we want to include.”
Weissman and his collaborators are not the only ones hoping to move a Zika vaccine from the lab to the clinic. A number of different groups have worked to develop a Zika vaccine over the last year. A Phase I clinical trial, to investigate vaccine safety, began last August of a DNA vaccine developed at the National Institutes of Health. And while investigators are hopeful that one of the vaccines in development could be ready for use by 2018, vaccines for pregnant women may be delayed until several years after that, due to the difficulties of demonstrating safety in that population.
The components of the mRNA vaccine also provide hope the vaccine could be used during pregnancy. Weissman explains, “The RNA they use is identical to what’s in our bodies. The nanoparticles also contain mostly physiological lipids. We’ve seen no adverse events from any of our immunizations, so we’re thinking that will probably be easy to give to a pregnant woman.”