Dengue virus (DENV) is the causative agent of dengue fever and dengue hemorrhagic fever. The virus is endemic in over 120 countries, causing over 350 million infections per year.
Dengue vaccine development is challenging because of the need to induce simultaneous protection against four antigenically distinct DENV serotypes and evidence that, under some conditions, vaccination can enhance disease due to specific immunity to the virus. While several live-attenuated tetravalent dengue virus vaccines display partial efficacy, it has been challenging to induce balanced protective immunity to all 4 serotypes. Instead of using whole-virus formulations, we are exploring the potentials for a particulate subunit vaccine, based on DENV E-protein displayed on nanoparticles that have been precisely molded using Particle Replication in Non-wetting Template (PRINT) technology.
Here we describe immunization studies with a DENV2-nanoparticle vaccine candidate. The ectodomain of DENV2-E protein was expressed as a secreted recombinant protein (sRecE), purified and adsorbed to poly (lactic-co-glycolic acid) (PLGA) nanoparticles of different sizes and shape. We show that PRINT nanoparticle adsorbed sRecE without any adjuvant induces higher IgG titers and a more potent DENV2-specific neutralizing antibody response compared to the soluble sRecE protein alone. Antigen trafficking indicate that PRINT nanoparticle display of sRecE prolongs the bio-availability of the antigen in the draining lymph nodes by creating an antigen depot. Our results demonstrate that PRINT nanoparticles are a promising platform for delivering subunit vaccines against flaviviruses such as dengue and Zika.
Dengue virus (DENV) is transmitted by mosquitoes and is endemic in over 120 countries, causing over 350 million infections yearly. Most infections are clinically unapparent, but under specific conditions, dengue can cause severe and lethal disease. DENV has 4 distinct serotypes and secondary DENV infections are associated with hemorrhagic fever and dengue shock syndrome. This enhancement of infection complicates vaccine development and makes it necessary to induce protective immunity against all 4 serotypes. Since whole virus vaccine candidates struggle to induce protective immunity, we are developing a nanoparticle display vaccine approach. We have expressed, purified and characterized a soluble recombinant E-protein (sRecE). Regardless of nanoparticle shape or size, particulation of sRecE enhances DENV specific IgG titers and induces a robust, long lasting neutralizing antibody response and by adsorbing sRecE to the nanoparticles, we prolong the exposure of sRecE to the immune system.
Nanoparticle display shows great promise in dengue vaccine development and possibly other mosquito-borne viruses like zika virus.
The Latest on: Nanoparticle vaccines
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The Latest on: Nanoparticle vaccines
- OSU researcher to help create gonorrhea vaccine on April 17, 2019 at 9:14 pm
She’ll also be in charge of a project that will study incorporating antigens into nanoparticle platforms called nanodiscs, an attempt to increase vaccine potency and efficacy. In addition to OSU and ... […]
- First-In-Human Trial Begins On Universal Flu Vaccine, Older Adults Still Encouraged To Vaccinate on April 16, 2019 at 7:20 am
A team of VRC scientists developed the vaccine prototype. “It displays part of hemagglutinin (HA), an influenza protein, on the surface of a microscopic nanoparticle made of nonhuman ferritin,” the ... […]
- Novavax: I'll Take Capitulation And Despondency Before Hope on April 14, 2019 at 1:50 pm
The company has also attempted to develop RSV vaccines for adults and another for healthy children between 2-6 years of age. Additionally, the company has tried to develop a nanoparticle vaccine ... […]
- Novavax Scientific Leadership to Present RSV Maternal Immunization Program Phase 3 Data and Participate in Panel on COPD at World Vaccine Congress on April 9, 2019 at 7:14 pm
Details are as follows: About ResVax™ ResVax is an RSV fusion (F) protein recombinant nanoparticle vaccine with aluminum phosphate as an adjuvant. Novavax is developing ResVax to protect infants ... […]
- First Human Trial of Universal Flu Vaccine Underway on April 7, 2019 at 7:29 am
"A team of VRC scientists developed the universal influenza vaccine prototype. It displays part of hemagglutinin (HA), an influenza protein, on the surface of a microscopic nanoparticle made of ... […]
- First-In-Human Trial of a Universal Influenza Vaccine Candidate Begins, NIH Reports on April 5, 2019 at 6:54 pm
Initial data from an earlier VRC clinical trial evaluating a ferritin nanoparticle vaccine that included both hemagglutinin head and stem showed that the platform is safe and well-tolerated in humans. […]
- NIH begins first-in-human trial of universal influenza vaccine candidate on April 5, 2019 at 2:30 am
It displays part of hemagglutinin (HA), an influenza protein, on the surface of a microscopic nanoparticle made of nonhuman ferritin. Ferritin is a natural protein that can be found in cells from all ... […]
- NIH Begins Trial of Potential Universal Flu Vaccine on April 4, 2019 at 9:24 am
H1ssF_3928 displays part of hemagglutinin (HA), an influenza protein, on the surface of a microscopic nanoparticle made of nonhuman ferritin, NIH said in a statement. Ferritin is a natural protein ... […]
- NIH unveils a vaccine candidate for universal flu jab as first-in-human studies get underway on April 4, 2019 at 4:32 am
The new vaccine ditches the head entirely in favor of the stem, which is more constant among different influenza strains. The HA stem is tagged onto a microscopic nanoparticle made of nonhuman ... […]
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