Nanoparticle vaccinates mice against dengue fever

October 20, 2016
This transmission electron micrograph (TEM) depicts a number of round, Dengue virus particles that were revealed in this tissue specimen. Credit: CDC/ Frederick Murphy

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 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 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."

Explore further: Zika infection is caused by one virus serotype, study finds

More information: Stefan W. Metz et al, Precisely Molded Nanoparticle Displaying DENV-E Proteins Induces Robust Serotype-Specific Neutralizing Antibody Responses, PLOS Neglected Tropical Diseases (2016). DOI: 10.1371/journal.pntd.0005071

Related Stories

Study could lead to vaccines and treatment for dengue virus

July 2, 2015
Researchers at Vanderbilt University and the National University of Singapore have determined the structure of a human monoclonal antibody which, in an animal model, strongly neutralizes a type of the potentially lethal dengue ...

A protein vaccine designed to target all four variations of the dengue virus proves effective in mouse trials

September 11, 2015
A breakthrough in the search for safe immunization against dengue fever has emerged after trials at A*STAR showed a new vaccine without live viruses induces an effective immune response.

Team finds powerful dengue neutralizing antibody

February 20, 2015
A new Duke-NUS-led study has identified a super-potent antibody which requires a minute amount to neutralize the dengue virus.

Human antibody for dengue virus isolated

June 22, 2012
(Phys.org) -- A group of scientists in Singapore and the UK have isolated a human antibody capable of effectively neutralizing the mosquito-borne dengue virus. Dengue fever is currently incurable and infects an estimated ...

Study finds viral protein that causes dengue shock

September 9, 2015
Scientists at the University of California, Berkeley, have identified a key culprit responsible for the fluid loss and resulting shock that are the hallmark of severe - and potentially fatal - dengue virus infections.

Recommended for you

H7N9 influenza is both lethal and transmissible in animal model for flu

October 19, 2017
In 2013, an influenza virus that had never before been detected began circulating among poultry in China. It caused several waves of human infection and in late 2016, the number of people to become sick from the H7N9 virus ...

Flu simulations suggest pandemics more likely in spring, early summer

October 19, 2017
New statistical simulations suggest that Northern Hemisphere flu pandemics are most likely to emerge in late spring or early summer at the tail end of the normal flu season, according to a new study published in PLOS Computational ...

Migraines may be the brain's way of dealing with oxidative stress

October 19, 2017
A new perspective article highlights a compelling theory about migraine attacks: that they are an integrated mechanism by which the brain protects and repairs itself. Recent insightful findings and potential ways to use them ...

New insights into herpes virus could inform vaccine development

October 18, 2017
A team of scientists has discovered new insights into the mechanisms of Epstein-Barr virus (EBV) infection, as well as two antibodies that block the virus' entry into cells. The findings, published in Proceedings of the National ...

Pair of discoveries illuminate new paths to flu and anthrax treatments

October 17, 2017
Two recent studies led by biologists at the University of California San Diego have set the research groundwork for new avenues to treat influenza and anthrax poisoning.

Portable 3-D scanner assesses patients with elephantiasis

October 17, 2017
An estimated 120 million people worldwide are infected with lymphatic filariasis, a parasitic, mosquito-borne disease that can cause major swelling and deformity of the legs, a condition known as elephantiasis. Health-care ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.