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
- Acuitas, CureVac settle lawsuit over COVID-19 vaccine patent rightson April 25, 2024 at 2:27 pm
Biotech company Acuitas Therapeutics and Germany-based CureVac have settled Acuitas' lawsuit demanding credit for inventions related to COVID-19 vaccines, according to a filing on Thursday in Virginia ...
- Cows' milk particles used for effective oral delivery of drugson April 24, 2024 at 11:16 am
Researchers have found that tiny particles present in cows' milk could offer, for the first time, an effective method for the oral delivery of RNA drugs.
- Moderna Investors Should Beware Patent-Dispute Fallouton April 23, 2024 at 11:40 am
Moderna's stock soared on positive cancer vaccine trial results, but legal troubles loom as a patent dispute threatens massive damages. Read my analysis here.
- Moderna gets grant for vaccine composition for varicella zoster viruson April 23, 2024 at 6:00 am
Discover how Moderna's groundbreaking patent for a nucleic acid vaccine targeting varicella zoster virus could revolutionize immunization. Learn about the innovative mRNA and lipid nanoparticle ...
- Engineering Powerful Vaccines with Lipid Nanotechnologyon April 21, 2024 at 6:15 am
In this, lipid nanoparticle (LNP) technology has emerged as highly promising. Progress in medical science has facilitated the seamless integration of lipid nanotechnology into standard therapy, ...
- New vaccine promises broad protection against SARS-CoV-2 and other sarbecoviruseson April 17, 2024 at 7:41 pm
Researchers at Georgia Tech and the University of Wisconsin have created a broad-spectrum vaccine capable of defending against various SARS-CoV-2 variants and related bat coronaviruses.
- Pfizer, BioNTech Get Legal Pause in Moderna’s COVID-19 Vaccine Patent Lawsuiton April 16, 2024 at 5:54 am
A federal court in Massachusetts has granted Pfizer and BioNTech’s motion to put on hold Moderna’s lawsuit over alleged patent infringement related to their COVID-19 vaccine Comirnaty.
- Toward A Universal Covid Vaccineon April 10, 2024 at 9:54 am
Over time, the virus develops a series of mutations in the Spike protein and other genes that aid in immune evasion, resulting in a new variant and reduced efficacy for the latest vaccine. The need ...
- ‘Naked mRNA’ Vaccines: A Safer Alternative to Lipid Nanoparticle Deliveryon April 2, 2024 at 4:59 pm
“Naked” Vaccine: Uchida Lab pioneers a groundbreaking approach, demonstrating robust vaccination against SARS-CoV-2 in mice and primates using intradermal administration of mRNA alone, without lipid ...
via Bing News