Nanoparticle vaccinates mice against dengue fever

October 20, 2016

Every year, more than 350 million people in over 120 countries contact dengue fever, which can cause symptoms ranging from achy muscles and a skin rash to life-threatening hemorrhagic fever. Researchers have struggled to create effective vaccines against dengue virus, in part because four distinct serotypes, or strains, cause the disease and a vaccine must immunize against all four individually. Now, a new type of nanoparticle, described in PLOS Neglected Tropical Diseases, effectively vaccinated mice against one of the serotypes and could be created to target all four.

Attempts at using live dengue viruses to develop a dengue fever vaccine have often led to an imbalance in immunity to the four dengue serotypes--for instance, one recent candidate had lower efficacy against serotype 2. Previous infection with one serotype of dengue, or protection against just one serotype, can lead to more severe disease if a person contracts other serotypes, so it's vital that vaccines are available that specifically target all four strains.

To create a new dengue virus vaccine, Stefan Metz, Shaomin Tian in the laboratories of Aravinda de Silva, Chris Luft and Joe DeSimone at the University of Carolina, Chapel Hill, USA designed nanoparticles of various shapes and sizes using Particle Replication in Non-wetting Template (PRINT) technology. Each nanoparticle was studded with copies of DENV2-E protein, a key protein from serotype 2 of the virus. Then, the researchers immunized 31 mice with a control injection or one of five different formulations of the nanoparticle, each with different size particles ranging from 55x70 nanometers to 200x200 nanometers. During the course of the immunizations, as well as four times after two boosters had been given, the researchers drew blood from the mice to follow their immune responses. Bone marrow and lymph node samples were also taken at various points after immunization.

After immunization with the DENV2-E nanoparticles, mice had a specific antibody response to serotype 2 of the dengue virus, but not the other three serotypes. Compared to mice vaccinated with only the soluble DENV2-E proteins, the nanoparticle formulations led to a stronger immune response. Although previous studies of similar nanoparticles have found an effect of nanoparticle shape and size on antibody responses, such a trend was not seen at significant levels for the DENV2-E vaccine. Future studies will be required to test whether the antibody levels prevent dengue infection as well as whether similar nanoparticles can be develop for all dengue serotypes.

"Though only focusing on DENV2, these findings form the basis of a safe and efficacious dengue virus candidate," the authors say. "In addition, this platform can be used to develop safe vaccine candidates for other flaviviruses such as Zika virus, where pregnant women are the target group for vaccination."
-end-
Please contact plosntds@plos.org if you would like more information about our content and specific topics of interest.

All works published in PLOS Neglected Tropical Diseases are open access, which means that everything is immediately and freely available. Use this URL in your coverage to provide readers access to the paper upon publication:

http://dx.plos.org/10.1371/journal.pntd.0005071 (Link goes live upon article publication)

Funding: This study was funded by US National Institutes of Health grant U19 AI109784-01. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing Interests: MS and KH hare employed by the commercial company Liquidia Technologies. JD is a founder and maintains a financial interest in Liquidia Technologies.

PLOS

Related Nanoparticles Articles from Brightsurf:

An ionic forcefield for nanoparticles
Nanoparticles are promising drug delivery tools but they struggle to get past the immune system's first line of defense: proteins in the blood serum that tag potential invaders.

Phytoplankton disturbed by nanoparticles
Products derived from nanotechnology are efficient and highly sought-after, yet their effects on the environment are still poorly understood.

How to get more cancer-fighting nanoparticles to where they are needed
University of Toronto Engineering researchers have discovered a dose threshold that greatly increases the delivery of cancer-fighting drugs into a tumour.

Nanoparticles: Acidic alert
Researchers of Ludwig-Maximilians-Universitaet (LMU) in Munich have synthesized nanoparticles that can be induced by a change in pH to release a deadly dose of ionized iron within cells.

3D reconstructions of individual nanoparticles
Want to find out how to design and build materials atom by atom?

Directing nanoparticles straight to tumors
Modern anticancer therapies aim to attack tumor cells while sparing healthy tissue.

Sweet nanoparticles trick kidney
Researchers engineer tiny particles with sugar molecules to prevent side effect in cancer therapy.

A megalibrary of nanoparticles
Using straightforward chemistry and a mix-and-match, modular strategy, researchers have developed a simple approach that could produce over 65,000 different types of complex nanoparticles.

Dialing up the heat on nanoparticles
Rapid progress in the field of metallic nanotechnology is sparking a science revolution that is likely to impact all areas of society, according to professor of physics Ventsislav Valev and his team at the University of Bath in the UK.

Illuminating the world of nanoparticles
Scientists at the Okinawa Institute of Science and Technology Graduate University (OIST) have developed a light-based device that can act as a biosensor, detecting biological substances in materials; for example, harmful pathogens in food samples.

Read More: Nanoparticles News and Nanoparticles Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.