title: Antigen sparing and enhanced protection using a novel rOv-ASP-1 adjuvant in aqueous formulation with influenza vaccines.
abstract: Influenza is one of the most common infectious diseases endangering the health of humans, especially young children and the elderly. Although vaccination is the most effective means of protection against influenza, frequent mutations in viral surface antigens, low protective efficacy of the influenza vaccine in the elderly, slow production process and the potential of vaccine supply shortage during a pandemic are significant limitations of current vaccines. Adjuvants have been used to enhance the efficacy of a variety of vaccines; however, no adjuvant is included in current influenza vaccines approved in the United States. In this study, we found that a novel adjuvant, rOv-ASP-1, co-administrated with inactivated influenza vaccine using an aqueous formulation, substantially improved the influenza-specific antibody response and protection against lethal infection in a mouse model. rOv-ASP-1 enhanced the magnitude of the specific antibody response after immunization with low doses of influenza vaccine, allowing antigen-sparring by 10-fold. The rOv-ASP-1 formulated vaccine induced a more rapid response and a stronger Th1-associated antibody response compared to vaccine alone and to the vaccine formulated with the adjuvant alum. Importantly, rOv-ASP-1 significantly enhanced cross-reactive antibody responses and protection against challenge with an antigenically distinct strain. These results demonstrate that rOv-ASP-1 is an effective adjuvant that: (1) accelerates and enhances the specific antibody response induced by influenza vaccine; (2) allows for antigen sparing; and (3) augments a Th1-biased and cross-reactive antibody response that confers protection against an antigenically distinct strain.
authors.affiliation: Department of Biology, Drexel University, 3245 Chestnut Street, Philadelphia, PA 19104, USA; DMX Inc., West Chester, PA 19382, USA.
authors.forename: Jiu
authors.initials: J
authors.lastname: Jiang
authors.affiliation: Department of Biology, Drexel University, 3245 Chestnut Street, Philadelphia, PA 19104, USA.
authors.forename: Erin M
authors.initials: EM
authors.lastname: Fisher
authors.affiliation: The Wistar Institute, Philadelphia, PA 19104, USA.
authors.forename: Scott E
authors.initials: SE
authors.lastname: Hensley
authors.affiliation: Lindsley F. Kimball Research Institute, New York Blood Center, New York, NY 10065, USA.
authors.forename: Sara
authors.initials: S
authors.lastname: Lustigman
authors.affiliation: Department of Biology, Drexel University, 3245 Chestnut Street, Philadelphia, PA 19104, USA. Electronic address: donna.murasko@drexel.edu.
authors.forename: Donna M
authors.initials: DM
authors.lastname: Murasko
authors.affiliation: Department of Microbiology, University of Pennsylvania Perelman School of Medicine, 3610 Hamilton Walk, Philadelphia, PA 19104, USA. Electronic address: hshen@mail.med.upenn.edu.
authors.forename: Hao
authors.initials: H
authors.lastname: Shen
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D000917:Antibody Formation; D000947:Antigens, Helminth / Q000494:pharmacology; D003429:Cross Reactions; D005260:Female; D015801:Helminth Proteins / Q000494:pharmacology; D007074:Immunoglobulin G / Q000097:blood; D053118:Influenza A Virus, H1N1 Subtype; D007252:Influenza Vaccines / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000517:prevention & control*; D018417:Th1 Cells / Q000276:immunology; D015164:Vaccines, Inactivated / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D000947:Antigens, Helminth; D015801:Helminth Proteins; D007074:Immunoglobulin G; D007252:Influenza Vaccines; C414408:Ov-ASP-1 protein, Onchocerca volvulus; D015164:Vaccines, Inactivated; C510903:fluarix
keywords: Adjuvant; Influenza; Vaccine; Virus