Authors: Martha Powell, Future Science Group
New collaborative research, led by scientists from the University of Pennsylvania (PA, USA), has pioneered an mRNA-based Zika vaccine with the potential to protect against the virus after a single dose. Preclinical trials demonstrated rapid and durable protective immunity in mice and macque monkeys, and the team hope these positive findings will continue moving forwards.
In the wake of recent Zika outbreaks in Latin America creating a vaccine has been high priority. The study, published recently in Nature, is the first to present a vaccine that doesn’t utilize a live virus but still produces potent and durable protection in animal models.
The new vaccine candidate consists of lipid nanoparticle-encapsulated nucleoside-modified mRNA delivered by injection. The mRNA utilized encodes two key viral proteins, the pre-membrane and the envelope protein, from a Zika virus strain isolated in 2013. The injected mRNA stimulates production of viral proteins by host cells, mimicking the immune response produced by a live-virus vaccine but avoiding many of the disadvantages.
For example, currently an adenovirus-based strategy is the only Zika vaccine candidate that has also demonstrated protective immunity in monkeys with a single dose. However, adenoviruses can be targeted by the immune system, in some cases neutralizing them before they can stimulate a protective response.
Lead author Drew Weissman (University of Pennsylvania) commented: “Our work so far suggests that this new vaccine strategy induces a level of virus neutralization about 25 times greater, after a single dose, than one sees in standard vaccines,”
“If a vaccine is effective after just a single immunization, the infrastructure needed for its administration can be much simpler. Production of an mRNA-based vaccine is also likely to be easier and less expensive compared to traditional virus- or viral protein-based vaccines.”
The researchers demonstrated in mice that a single injection of 30 μg induced an immune response that protected the mouse from exposure to a separate strain of Zika virus at both 2 weeks and 5 months post-vaccination. Moreover, in maque monkeys a dose of 50 μg provided protection 5 weeks after initial vaccination.
The team cites strong stimulation of CD4 T helper cells as the cause of this potent and durable neutralizing antibody response. It is not known how long protective levels of immunity could last, however this novel approach provides a promising vaccine candidate in the fight against Zika virus.
Weissman concluded: “We observed rapid and durable protective immunity without adverse events, and so we think this candidate vaccine represents a promising strategy for the global fight against Zika virus. We hope to start clinical trials in 12 to 18 months.”
Source: Pardi N, Hogan MJ, Pelc RS et al. Zika virus protection by a single low-dose nucleoside-modified mRNA vaccination, Nature. doi:10.1038/nature21428 (2017) (Epub ahead of print) www.pennmedicine.org/news/news-releases/2017/february/new-zika-vaccine-candidate-protects-mice-and-monkeys-with-a-single-dose