Novel Recombinant Rabies Vaccine Also Capable of Immunocontraception

This invention relates to a recombinant, attenuated rabies vaccine that is also capable of inhibiting reproductive fertility. An Evelyn-Rokitnicki-Abelseth (ERA) rabies vaccine backbone, combined with a reproductive-specific protein, such as gonadotropin-releasing hormone (GnRH) or the sperm-binding zona-pellucida-glycoprotein-3 (ZP3) receptor, allows reduction in both rabies transmission and uncontrolled reproduction in stray animals. The ERA rabies vaccine backbone has previously shown strong efficacy in animal studies.

Novel Live-Attenuated Rabies Vaccine

The critical feature of this technology is the Evelyn-Rokitnicki-Abelseth (ERA) rabies whole genome DNA sequence. With the availability of the entire rabies genome, a recombinant vaccine can be developed using reverse genetics. Using this technology, CDC researchers have developed a recombinant, live-attenuated vaccine shown to confer protection against lethal doses of live, street-rabies virus in multiple survival studies. This vaccine offers better protection than traditional inactivated vaccinations, as demonstrated in co-infection studies.

Antigen-capture Electrochemiluminescent Assay for Determining Rabies Vaccine Potency

CDC researchers developed a more efficient method of assessing rabies vaccine potency using an antigen-capture electrochemiluminescent (ECL) assay. This assay utilizes SULFO-NHS-Ester labeled murine monoclonal antibodies to quantify glycoprotein concentration, which is an indicator of vaccine potency. Currently, the potency of rabies vaccines is determined by the effective-dose (ED50) mouse study evaluation method, which is more than 50 years old.

Recombinant Pan-Lyssavirus for Use in Rabies and Broad-Lyssavirus Vaccination

CDC researchers have developed recombinant lyssaviruses that can be used for the development of an improved, broad-spectrum vaccine against several rabies genotypes. Lyssaviruses are single-stranded RNA viruses that cause rabies and rabies-like diseases in mammals. Currently, there are commercially available vaccines that are considered to be effective against infections from a single viral phylogroup; however, these vaccines confer little or no protection against viruses outside of the phylogroup.

Reduced Virulence Crimean-Congo Hemorrhagic Fever Virus for Vaccine Development

This invention relates to a genetically modified hemorrhagic fever virus that can be used as an effective live vaccine agent. Hemorrhagic fever evades the human immune response using the viral ovarian tumor domain (vOTU) protease, which inhibits critical host-immunity functions. The present genetically modified virus has a vOTU protease with decreased ability to remove ubiquitin (Ub) and ISG15 tags from proteins in cells it infects. Thus, the virulence is reduced, creating an immunogenic and non-pathogenic virus for use as a live vaccine against Crimean-Congo hemorrhagic fever (CCHF) virus.

Use of Vitronectin as a Biomarker for the Detection of Dengue Hemorrhagic Fever

Dengue hemorrhagic fever (DHF) is a severe, potentially deadly infection spread by mosquitos. CDC scientists have identified vitronectin as an important biomarker of DHF. They have shown vitronectin is significantly reduced in DHF and severe dengue infections when compared to dengue non-hemorrhagic fever patients. Presently, DHF is established by assessing antibody concentrations and other rule-of-thumb criteria, but often these assays can be difficult to interpret and lead to false conclusions.

Multiplex Assay for Detection of Dengue Virus

Dengue virus (DENV) is the cause of dengue illness (dengue fever, dengue hemorrhagic fever, and dengue shock syndrome). CDC researchers have developed a RT-PCR multiplex assay that, prior to sero-conversion, selectively detects dengue virus in biological or other fluid media, such as whole blood, plasma, or serum. The primers and probes from this assay are sufficiently specific to amplify and detect all four DENV serotypes. This FDA-approved technology may provide an improved method for rapid and accurate serotyping of dengue virus in clinical and research settings.

Full-Length cDNA Clone Representing the Consensus Sequence of the RNA Genome of a Human Norovirus (strain MD145-12) That Encodes Biologically Active Proteins

The invention provides for a full-length cloned cDNA copy of the RNA genome of a predominant norovirus strain (Genogroup II.4) designated MD145-12 that was associated with human gastrointestinal illness. The noroviruses, which were formerly known as "Norwalk-like" viruses are estimated to cause 23 million cases of acute gastroenteritis in the USA each year. The virus has been designated into category B of the CDC biodefense-related priority pathogens because it can be used as an agent of bioterrorism.

A Broadly Protective Human Antibody for GI Genogroup Noroviruses

Norovirus is a leading cause of vomiting, diarrhea, and foodborne illness worldwide, with 700 million cases and 200,000 deaths occurring each year. Despite decades of work in the field, there are no preventive or therapeutic strategies specifically approved for even the most prevalent forms of human norovirus (i.e., GI, GII genogroups), which are highly contagious and carry an increased risk of severe complications in children, older adults, and those with immunocompromising conditions. 

A Novel Strategy to Produce 6-cys Proteins Based on Pfs230D1 Domain Fusions

The Plasmodium parasite has a complex lifecycle during human infection and in the mosquito vector. Most advanced malaria vaccine candidates can confer only partial, short-term protection in malaria-endemic areas. A means of breaking the transmission of malaria to subsequent individuals could prevent a significant amount of human disease.

The primary embodiments of this technology are novel compositions of matter that produce enhanced transmission-blocking responses over current transmission blocking vaccines:

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