title: The Carbomer-Lecithin Adjuvant Adjuplex Has Potent Immunoactivating Properties and Elicits Protective Adaptive Immunity against Influenza Virus Challenge in Mice.
abstract: The continued discovery and development of adjuvants for vaccine formulation are important to safely increase potency and/or reduce the antigen doses of existing vaccines and tailor the adaptive immune response to newly developed vaccines. Adjuplex is a novel adjuvant platform based on a purified lecithin and carbomer homopolymer. Here, we analyzed the adjuvant activity of Adjuplex in mice for the soluble hemagglutinin (HA) glycoprotein of influenza A virus. The titration of Adjuplex revealed an optimal dose of 1% for immunogenicity, eliciting high titers of HA-specific IgG but inducing no significant weight loss. At this dose, Adjuplex completely protected mice from an otherwise lethal influenza virus challenge and was at least as effective as the adjuvants monophosphoryl lipid A (MPL) and alum in preventing disease. Adjuplex elicited balanced Th1-/Th2-type immune responses with accompanying cytokines and triggered antigen-specific CD8(+) T-cell proliferation. The use of the peritoneal inflammation model revealed that Adjuplex recruited dendritic cells (DCs), monocytes, and neutrophils in the context of innate cytokine and chemokine secretion. Adjuplex neither triggered classical maturation of DCs nor activated a pathogen recognition receptor (PRR)-expressing NF-κB reporter cell line, suggesting a mechanism of action different from that reported for classical pathogen-associated molecular pattern (PAMP)-activated innate immunity. Taken together, these data reveal Adjuplex to be a potent and well-tolerated adjuvant with application for subunit vaccines.
authors.affiliation: The Sir William Dunn School of Pathology, The University of Oxford, Oxford, United Kingdom Janssen Infectious Diseases and Vaccines, Leiden, The Netherlands.
authors.forename: Frank
authors.initials: F
authors.lastname: Wegmann
authors.affiliation: The Sir William Dunn School of Pathology, The University of Oxford, Oxford, United Kingdom.
authors.forename: Amin E
authors.initials: AE
authors.lastname: Moghaddam
authors.affiliation: The Sir William Dunn School of Pathology, The University of Oxford, Oxford, United Kingdom.
authors.forename: Torben
authors.initials: T
authors.lastname: Schiffner
authors.affiliation: The Sir William Dunn School of Pathology, The University of Oxford, Oxford, United Kingdom.
authors.forename: Kate H
authors.initials: KH
authors.lastname: Gartlan
authors.affiliation: Molecular Immunology Group, MRC Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom.
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Powell
authors.affiliation: The Sir William Dunn School of Pathology, The University of Oxford, Oxford, United Kingdom.
authors.forename: Rebecca A
authors.initials: RA
authors.lastname: Russell
authors.affiliation: Janssen Infectious Diseases and Vaccines, Leiden, The Netherlands.
authors.forename: Matthijs
authors.initials: M
authors.lastname: Baart
authors.affiliation: Advanced BioAdjuvants, Omaha, Nebraska, USA.
authors.forename: Emily W
authors.initials: EW
authors.lastname: Carrow
authors.affiliation: The Sir William Dunn School of Pathology, The University of Oxford, Oxford, United Kingdom quentin.sattentau@path.ox.ac.uk.
authors.forename: Quentin J
authors.initials: QJ
authors.lastname: Sattentau
mesh_terms: D000180:Acrylic Resins; D056704:Adaptive Immunity; D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000276:immunology*; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology*; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000276:immunology*; D054709:Lecithins / Q000276:immunology; D008807:Mice, Inbred BALB C; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000517:prevention & control*; D000069452:Pathogen-Associated Molecular Pattern Molecules; D058408:Th1-Th2 Balance; D014611:Vaccination
chemical_list: D000180:Acrylic Resins; D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D016207:Cytokines; C543345:H1N1 virus hemagglutinin; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007252:Influenza Vaccines; D054709:Lecithins; D000069452:Pathogen-Associated Molecular Pattern Molecules; C479038:carbomer