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
- Novavax to Present at the H.C. Wainwright 21st Annual Global Investment Conferenceon September 6, 2019 at 4:11 am
Novavax is also advancing NanoFlu™, its quadrivalent influenza nanoparticle vaccine, to address key factors that can lead to the poor effectiveness of currently approved flu vaccines.
- Novavax, Inc.: Novavax to Present at the H.C. Wainwright 21st Annual Global Investment Conferenceon September 6, 2019 at 4:05 am
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Our results show that the hybrid T4-AAV vector can function both as a gene delivery vehicle, eliciting transgene expression, and as a vaccine, eliciting robust immune responses. This might be because ...
- Israeli-Portuguese-Italian team develops advanced vaccine for melanomaon August 9, 2019 at 12:05 pm
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- Novel nano-vaccine for melanoma developedon August 6, 2019 at 4:45 am
The focus of the research, published in the journal Nature Nanotechnology, is on a nanoparticle that serves as the basis for the new vaccine. Melanoma develops in the skin cells that produce melanin ...
- Scientists demonstrate a new nano-vaccine preventing the spread of melanomaon August 5, 2019 at 9:41 pm
Developed by scientists at Tel Aviv University, the prospective vaccine encases two experimental new cancer drugs inside a tiny nanoparticle, with initial experiments revealing the therapy can both ...
- Tel Aviv researchers develop a nano-vaccine for the most aggressive skin canceron August 5, 2019 at 7:58 pm
The focus of the research is on a nanoparticle that serves as the basis for the new vaccine. The study was led by Prof. Ronit Satchi-Fainaro, chair of the Department of Physiology and Pharmacology and ...
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