Recombinant VP4 Polypeptides as Antigens for a Rotavirus Vaccine
Inventors: Stephen Harrison, Philip Dormitzer, Joshua Yoder, Harry Greenberg
Invention Types: Therapeutics
Research Areas: Gastrointestinal/Nutrition
Keywords: VaccineFor More Information Contact: Meyer, Abbie
The invention provides a novel structure-based approach for the design of specific, safe and stable vaccine against rotavirus infections. The invention is based on the high-resolution structural data of fragments of the rotavirus neutralizing antigen VP4 and the specific engineering of these polypeptides, or the nucleic acids that encode them, into the vaccines.
The invention has applications in the treatment of the most common cause of severe vomiting and diarrhea in children worldwide. The methods and polypeptides presented in this invention could be applied in the diagnosis, treatment and prevention of rotavirus infections. Recombinant VP4 polypeptides can be used as antigens for vaccine development.
The structure-based molecular engineering approach has major advantages over other techniques of vaccine design used today. These include safety, high degree of specificity, proper conformation of epitopes and inexpensive generation of inherently non-infectious and gut-stable molecules. The invention provides a variety of molecules such as recombinant polypeptides and their fusions, fragments, variants and derivatives.
Key Publications: Dormitzer PR, et al. Proteolysis of monomeric recombinant rotavirus VP4 yields an oligomeric VP5* core. J Virol. 2001 Aug;75(16):7339-50.
Dormitzer PR, et al. The rhesus rotavirus VP4 sialic acid binding domain has a galectin fold with a novel carbohydrate binding site. EMBO J. 2002 Mar 1;21(5):885-97.
Yoder JD, et al. VP5* rearranges when rotavirus uncoats. J Virol. 2009 Nov;83(21):11372-7.
Trask SD, et al. A rotavirus spike protein conformational intermediate binds lipid bilayers. J Virol. 2010 Feb;84(4):1764-70.