title: Preclinical dose-ranging studies of a novel dry powder norovirus vaccine formulation.
abstract: Norovirus is the primary cause of viral gastroenteritis in humans with multiple genotypes currently circulating worldwide. The development of a successful norovirus vaccine is contingent on its ability to induce both systemic and mucosal antibody responses against a wide range of norovirus genotypes. Norovirus virus-like particles (VLPs) are known to elicit systemic and mucosal immune responses when delivered intranasally. Incorporation of these VLPs into an intranasal powder vaccine offers the advantage of simplicity and induction of neutralizing systemic and mucosal antibodies. Nasal immunization, which provides the advantage of ease of administration and a mucosal delivery mechanism, faces the real issue of limited nasal residence time due to mucociliary clearance. Herein, we describe a novel dry powder (GelVac™) formulation of GI or GII.4 norovirus VLPs, two dominant circulating genotypes, to identify the optimal antigen dosages based on systemic and mucosal immune responses in guinea pigs. Systemic and mucosal immunogenicity of each of the VLPs was observed in a dose-dependent manner. In addition, a boosting effect was observed after the second dosing of each VLP antigen. With the GelVac™ formulation, a total antigen dose of ≥ 15 μg was determined to be the maximally immunogenic dose for both GI and GII.4 norovirus VLPs based on evaluation for 56 days. Taken together, these results indicate that norovirus VLPs could be used as potential vaccine candidates without using an immunostimulatory adjuvant and provide a basis for the development of a GelVac™ bivalent GI/GII.4 norovirus VLP vaccine.
authors.affiliation: Research and Development Department, Nanotherapeutics, Inc., Alachua, FL, United States.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Springer
authors.affiliation: Research and Development Department, Nanotherapeutics, Inc., Alachua, FL, United States.
authors.forename: Yawei
authors.initials: Y
authors.lastname: Ni
authors.affiliation: Research and Development Department, Nanotherapeutics, Inc., Alachua, FL, United States.
authors.forename: Isaac
authors.initials: I
authors.lastname: Finger-Baker
authors.affiliation: Research and Development Department, Nanotherapeutics, Inc., Alachua, FL, United States.
authors.forename: Jordan P
authors.initials: JP
authors.lastname: Ball
authors.affiliation: Research and Development Department, Nanotherapeutics, Inc., Alachua, FL, United States.
authors.forename: Jessica
authors.initials: J
authors.lastname: Hahn
authors.affiliation: Research and Development Department, Nanotherapeutics, Inc., Alachua, FL, United States.
authors.forename: Ashley V
authors.initials: AV
authors.lastname: DiMarco
authors.affiliation: Toxicology Department, Battelle Memorial Institute, West Jefferson, OH, United States.
authors.forename: Dean
authors.initials: D
authors.lastname: Kobs
authors.affiliation: Battelle Eastern Science and Technology Center, Aberdeen, MD, United States.
authors.forename: Bobbi
authors.initials: B
authors.lastname: Horne
authors.affiliation: Research and Development Department, Nanotherapeutics, Inc., Alachua, FL, United States.
authors.forename: James D
authors.initials: JD
authors.lastname: Talton
authors.affiliation: Research and Development Department, Nanotherapeutics, Inc., Alachua, FL, United States. Electronic address: rcobb@nanotherapeutics.com.
authors.forename: Ronald R
authors.initials: RR
authors.lastname: Cobb
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D006168:Guinea Pigs; D018928:Immunity, Mucosal; D007074:Immunoglobulin G / Q000097:blood; D009500:Neutralization Tests; D029322:Norovirus; D011208:Powders; D011897:Random Allocation; D014611:Vaccination / Q000379:methods*; D058425:Vaccines, Virus-Like Particle / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology; D014765:Viral Vaccines / Q000008:administration & dosage* / Q000737:chemistry* / Q000276:immunology
chemical_list: D000914:Antibodies, Viral; D007074:Immunoglobulin G; D011208:Powders; D058425:Vaccines, Virus-Like Particle; D014765:Viral Vaccines
keywords: Guinea Pigs; Intranasal; Norovirus; Vaccine; Virus-like Particles