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.
Author Summary
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
[google_news title=”” keyword=”Nanoparticle vaccines” num_posts=”10″ blurb_length=”0″ show_thumb=”left”]
via Google News
The Latest on: Nanoparticle vaccines
- SEC recommends permission to SII for Omicron XBB 1.5 variant Covid-19 vaccineon May 9, 2024 at 10:53 pm
A Subject Expert Committee (SEC), which advices the national drug regulator on approvals and clinical trials related to Covid-19 vaccines, has recommended grant of permission to Serum Institute of ...
- Researchers develop mRNA vaccine to target aggressive brain canceron May 9, 2024 at 10:30 pm
Researchers from the University of Florida in the US developed an mRNA cancer vaccine which triggers the immune system to target the tumour. Approximately 19,000 individuals in th ...
- What does science say about mRNA vaccines for pigs?on May 9, 2024 at 10:00 pm
Any discussion about mRNA vaccines should be preceded by a decent biology lesson, otherwise an interested reader might well get lost before he or she even got started. After all, the article will ...
- New mRNA vaccine for deadly brain cancer triggers a strong immune responseon May 9, 2024 at 4:00 am
In clinical trials, the vaccine material is often packaged into tiny lipid nanoparticles, but the trials typically only deliver a small number of particles and the vaccines themselves take months, if ...
- How ‘Quartet Nanocage’ vaccine developed in Cambridge, Oxford and Caltech could provide broad protection against coronaviruses - including ones we don’t know exist yeton May 8, 2024 at 11:00 pm
A new vaccine technology effective in mice against a broad range of coronaviruses - including ones we do not even know about - has been developed by researchers. The scientists at the University of ...
- Innovative nanoparticle breaks blood-brain barrier to target breast cancer and brain metastaseson May 7, 2024 at 10:00 am
Researchers at Sylvester Comprehensive Cancer Center at the University of Miami Miller School of Medicine have developed a nanoparticle that can penetrate the blood-brain barrier.
- Our new vaccine could protect against coronaviruses that haven’t even emerged yet – new studyon May 7, 2024 at 7:53 am
The rapid development of vaccines that protect against COVID was a remarkable scientific achievement that saved millions of lives. The vaccines have demonstrated substantial success in reducing death ...
- Nanoparticle researchers develop microfluidic platform for better delivery of gene therapy for lung diseaseon May 7, 2024 at 7:14 am
Drug delivery researchers at Oregon State University have developed a device with the potential to improve gene therapy for patients with inherited lung diseases such as cystic fibrosis.
- Glioblastoma vaccine turns brain tumors from cold to hot in humans and dogson May 7, 2024 at 2:29 am
A personalized mRNA-based cancer vaccine for glioblastoma with an “onion-like” delivery mechanism can prolong survival both in dogs and humans, the results of a small study have suggested.
via Bing News