title: A recombinant rabies vaccine expressing the trimeric form of the glycoprotein confers enhanced immunogenicity and protection in outbred mice.
abstract: Rabies is a disease characterized by an invariably lethal encephalitis of viral origin that can be controlled by preventive vaccination programs of wildlife, domestic animals and humans in areas with a high risk of exposure. Currently available vaccines are expensive, cumbersome to produce and require intensive immunization and booster schemes to induce and maintain protective immunity. In the present study, we describe the development of candidate recombinant subunit rabies vaccines based on the glycoprotein G of the prototype rabies virus (RABV-G) expressed either as a monomer (RABV-mG) or in its native trimeric configuration (RABV-tG), with or without Matrix-M™ adjuvant. Immunogenicity and protective efficacy of the respective candidate vaccines were tested in outbred NIH Swiss albino mice. The RABV-tG candidate vaccine proved to be superior to the RABV-mG vaccine candidate both in terms of immunogenicity and efficacy. The relatively poor immunogenicity of the RABV-mG vaccine candidate was greatly improved by the addition of the adjuvant. A single, low dose of RABV-tG in combination with Matrix-M™ induced high levels of high avidity neutralizing antibodies and protected all mice against challenge with a lethal dose of RABV. Consequently RABV-tG used in combination with Matrix-M™ is a promising vaccine candidate that overcomes the limitations of currently used vaccines.
authors: Department of Viroscience, Erasmus Medical Centre, PO Box 2040, 3000 CA Rotterdam The Netherlands. Electronic address: p.koraka@erasmusmc.nl.
authors: Penelope
authors: P
authors: Koraka
authors: Virology Division, Department of Infectious Diseases & Immunology, Faculty of Veterinary Medicine, Utrecht University, 3508TD Utrecht, The Netherlands.
authors: Berend-Jan
authors: BJ
authors: Bosch
authors: Protein Sciences Corp, 1000 Research Parkway, Meriden, CT 06450-7159, USA.
authors: Manon
authors: M
authors: Cox
authors: Protein Sciences Corp, 1000 Research Parkway, Meriden, CT 06450-7159, USA.
authors: Rick
authors: R
authors: Chubet
authors: Department of Viroscience, Erasmus Medical Centre, PO Box 2040, 3000 CA Rotterdam The Netherlands; Institute for Translational Immunology, PO Box 450, 3720 AL Bilthoven, The Netherlands.
authors: Geert van
authors: Gv
authors: Amerongen
authors: Novavax AB, Kungsgatan 109, SE-753 18 Uppsala, Sweeden.
authors: Karen
authors: K
authors: Lövgren-Bengtsson
authors: Department of Viroscience, Erasmus Medical Centre, PO Box 2040, 3000 CA Rotterdam The Netherlands.
authors: Byron E E
authors: BE
authors: Martina
authors: Department of Viroscience, Erasmus Medical Centre, PO Box 2040, 3000 CA Rotterdam The Netherlands.
authors: Jouke
authors: J
authors: Roose
authors: Virology Division, Department of Infectious Diseases & Immunology, Faculty of Veterinary Medicine, Utrecht University, 3508TD Utrecht, The Netherlands.
authors: Peter J M
authors: PJ
authors: Rottier
authors: Department of Viroscience, Erasmus Medical Centre, PO Box 2040, 3000 CA Rotterdam The Netherlands.
authors: Albert D M E
authors: AD
authors: Osterhaus
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood; D000917:Antibody Formation; D000956:Antigens, Viral / Q000276:immunology*; D006023:Glycoproteins / Q000276:immunology*; D051379:Mice; D011818:Rabies / Q000517:prevention & control*; D011819:Rabies Vaccines / Q000276:immunology*; D011820:Rabies virus; D014614:Vaccines, Synthetic / Q000276:immunology; D014759:Viral Envelope Proteins / Q000276:immunology*
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D000956:Antigens, Viral; D006023:Glycoproteins; D011819:Rabies Vaccines; D014614:Vaccines, Synthetic; D014759:Viral Envelope Proteins; C064951:glycoprotein G, Rabies virus
keywords: Glycoprotein G; Matrix-M™; Rabies; Vaccine