title: Evaluation of nonspreading Rift Valley fever virus as a vaccine vector using influenza virus hemagglutinin as a model antigen.
abstract: Virus replicon particles are capable of infection, genome replication and gene expression, but are unable to produce progeny virions, rendering their use inherently safe. By virtue of this unique combination of features, replicon particles hold great promise for vaccine applications. We previously developed replicon particles of Rift Valley fever virus (RVFV) and demonstrated their high efficacy as a RVFV vaccine in the natural target species. We have now investigated the feasibility of using this nonspreading RVFV (NSR) as a vaccine vector using influenza virus hemagglutinin as a model antigen. NSR particles were designed to express either the full-length hemagglutinin of influenza A virus H1N1 (NSR-HA) or the respective soluble ectodomain (NSR-sHA). The efficacies of the two NSR vector vaccines, applied via either the intramuscular or the intranasal route, were evaluated. A single vaccination with NSR-HA protected all mice from a lethal challenge dose, while vaccination with NSR-sHA was not protective. Interestingly, whereas intramuscular vaccination elicited superior systemic immune responses, intranasal vaccination provided optimal clinical protection.
authors: Department of Virology, Central Veterinary Institute of Wageningen University and Research Centre, Lelystad, The Netherlands; Department of Infectious Diseases & Immunology, Virology Division, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands. Electronic address: nadia.oreshkova@wur.nl.
authors: N
authors: N
authors: Oreshkova
authors: Department of Virology, Central Veterinary Institute of Wageningen University and Research Centre, Lelystad, The Netherlands. Electronic address: Lisette.Cornelissen@wur.nl.
authors: L A H M
authors: LA
authors: Cornelissen
authors: Department of Infectious Diseases & Immunology, Virology Division, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands. Electronic address: C.A.M.deHaan@uu.nl.
authors: C A M
authors: CA
authors: de Haan
authors: Department of Virology, Central Veterinary Institute of Wageningen University and Research Centre, Lelystad, The Netherlands; Department of Infectious Diseases & Immunology, Virology Division, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands. Electronic address: rob.moormann@wur.nl.
authors: R J M
authors: RJ
authors: Moormann
authors: Department of Virology, Central Veterinary Institute of Wageningen University and Research Centre, Lelystad, The Netherlands. Electronic address: jeroen.kortekaas@wur.nl.
authors: J
authors: J
authors: Kortekaas
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D000956:Antigens, Viral / Q000276:immunology; D016207:Cytokines / Q000276:immunology; D005260:Female; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000276:immunology*; D007074:Immunoglobulin G / Q000097:blood; D053118:Influenza A Virus, H1N1 Subtype; D007252:Influenza Vaccines / Q000276:immunology*; D007273:Injections, Intramuscular; D008807:Mice, Inbred BALB C; D009976:Orthomyxoviridae Infections / Q000517:prevention & control*; D012093:Replicon / Q000276:immunology; D012296:Rift Valley fever virus / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D014611:Vaccination / Q000379:methods
chemical_list: D000914:Antibodies, Viral; D000956:Antigens, Viral; D016207:Cytokines; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007074:Immunoglobulin G; D007252:Influenza Vaccines
keywords: Hemagglutinin; Intranasal; Nonspreading; Rift Valley fever virus; Vaccine; Vector