Rift Valley Fever Virus glycoproteins, Gn and Gc, and their use
Inventors
Richt, Juergen A. • Faburay, Bonto • Wilson, William
Assignees
Kansas State University • US Department of Agriculture USDA
Publication Number
US-9791445-B2
Publication Date
2017-10-17
Expiration Date
2034-01-28
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Abstract
The present invention describes subunit vaccines containing Gn and Gc glycoproteins of the Rift Valley Fever Virus, including nucleic acids encoding such glycoproteins, host cells, vectors, and immunoreagents generated with the glycoproteins, methods of vaccination, methods of diagnosis, and kits.
Core Innovation
The invention discloses immunoreagents useful for treatment and diagnosis of Rift Valley Fever Virus (RVFV) infection, specifically subunit vaccines containing Gn and Gc glycoproteins of RVFV, nucleic acids encoding these glycoproteins, host cells, vectors, immunoreagents generated with these glycoproteins, methods of vaccination and diagnosis, and kits comprising these components.
RVFV is a mosquito-borne zoonotic pathogen causing high morbidity and mortality in both livestock and humans, with significant impact especially in young ruminants and increasing severe human cases. Current vaccines, including live attenuated or inactivated whole virus vaccines, have limitations such as teratogenicity and limited immunogenicity, and there are no fully approved vaccines outside endemic regions. Hence, there is an urgent need for safe, efficacious vaccines capable of inducing rapid protective immunity and that offer compatibility with differentiating infected from vaccinated animals (DIVA).
The invention addresses this need by providing isolated nucleic acids and proteins encoding and comprising the Gn and Gc RVFV glycoproteins, which are surface envelope proteins playing a role in virus attachment and eliciting production of neutralizing antibodies. The invention includes modified sequences to enhance expression and glycosylation, methods for expression using baculovirus in eukaryotic systems, and compositions that induce strong neutralizing antibody response, demonstrated in a natural host species (sheep). The vaccine induces protective neutralizing antibodies after a single dose, with strong anamnestic responses after boosting, while enabling DIVA-compatible diagnostics via lack of nucleocapsid (N) protein in the vaccine. The recombinant proteins also function as immunoreagents for disease diagnosis.
Claims Coverage
The patent includes one independent claim focusing on a specific isolated protein construct. The claims cover inventive features of the protein design and its immunogenic properties.
Isolated fusion protein comprising Gn glycoprotein sequence with C-terminal histidine tag
An isolated protein comprising a fusion protein containing an amino acid sequence as set forth in SEQ ID NO:4 (Gn ectodomain), wherein the carboxyl terminus of SEQ ID NO:4 is operatively linked to a protease cleavage site followed by six carboxyl-terminal histidine residues.
Protein inducing neutralizing antibodies at primary dose
The protein consists of the amino acid sequence of SEQ ID NO:4 operatively linked at the carboxyl terminal alanine to a protease cleavage site with six histidine residues. This protein induces neutralizing antibodies against Rift Valley Fever Virus in a subject at primary dose.
Use of specific protease cleavage site
The protease cleavage site is specified as the TENT protease site of a pFastBac/CT TOPO vector, enabling proper processing of the fusion protein.
The claims broadly cover an isolated Gn glycoprotein-based fusion protein containing a defined protease cleavage site and histidine tag, emphasizing its ability to induce neutralizing antibodies upon primary vaccination, representing the principal inventive features within the patent.
Stated Advantages
The vaccine candidate elicits a rapid onset of protective neutralizing antibody response within two weeks post single vaccination.
The vaccine is safe and highly immunogenic, eliciting strong immune responses in the natural host species (sheep).
The vaccine composition enables DIVA compatibility by excluding nucleocapsid protein, allowing differentiation of vaccinated from infected animals.
Use of modified signal peptides enhances protein glycosylation, thus improving antigenicity and immunogenicity of the glycoproteins.
Recombinant subunit vaccine avoids the biosafety risks and side effects associated with live attenuated vaccines.
Documented Applications
Subunit vaccines for immunization of ruminant animals, especially sheep, against Rift Valley Fever Virus.
Methods of vaccination administering immunogenically effective amounts of recombinant Gn and Gc proteins to induce neutralizing antibodies.
Diagnostic assays detecting Rift Valley Fever Virus infection or vaccination status using recombinant glycoproteins and nucleocapsid proteins in ELISA or immunoassays.
Reagents for production of monoclonal or polyclonal antibodies specific to RVFV glycoproteins for diagnostic use.
Kits comprising recombinant proteins, immunoreagents, buffers, and instructions for diagnosis or vaccination against RVFV.
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