title: Delta inulin-derived adjuvants that elicit Th1 phenotype following vaccination reduces respiratory syncytial virus lung titers without a reduction in lung immunopathology.
abstract: Respiratory syncytial virus (RSV) is a significant cause of lower respiratory tract infections resulting in bronchiolitis and even mortality in the elderly and young children/infants. Despite the impact of this virus on human health, no licensed vaccine exists. Unlike many other viral infections, RSV infection or vaccination does not induce durable protective antibodies in humans. In order to elicit high titer, neutralizing antibodies against RSV, we investigated the use of the adjuvant Advax™, a novel polysaccharide adjuvant based on delta inulin microparticles, to enhance antibody titers following vaccination. BALB/c mice were vaccinated intramuscularly with live RSV as a vaccine antigen in combination with one of two formulations of Advax™. Advax-1 was comprised of the standard delta inulin adjuvant and Advax-2 was formulated delta inulin plus CpG oligodendronucleotides (ODNs). An additional group of mice were either mock vaccinated, immunized with vaccine only, or administered vaccine plus Imject Alum. Following 3 vaccinations, mice had neutralizing antibody titers that correlated with reduction in viral titers in the lungs. Advax-1 significantly enhanced serum RSV-specific IgG1 levels at week 6 indicative of a Th2 response, similar to titers in mice administered vaccine plus Imject Alum. In contrast, mice vaccinated with vaccine plus Advax-2 had predominately IgG2a titers indicative of a Th1 response that was maintained during the entire study. Interestingly, regardless of which AdvaxTMadjuvant was used, the neutralizing titers were similar between groups, but the viral lung titers were significantly lower (∼10E+3pfu/g) in mice administered vaccine with either AdvaxTMadjuvant compared to mice administered adjuvants only. The lung pathology in vaccinated mice with AdvaxTMwas similar to Imject Alum. Overall, RSV vaccine formulated with AdvaxTMhad high neutralizing antibody titers with low lung viral titers, but exacerbated lung pathology compared to unvaccinated mice.
authors.affiliation: a Center for Vaccines and Immunology, Department of Infectious Diseases, University of Georgia , Athens , GA USA.
authors.forename: Terianne M
authors.initials: TM
authors.lastname: Wong
authors.affiliation: b Vaxine Pty Ltd., Flinders Medical Center , Adelaide , Australia.
authors.forename: Nikolai
authors.initials: N
authors.lastname: Petrovsky
authors.affiliation: c Department of Pathology , University of Pittsburgh , Pittsburgh , PA , USA.
authors.forename: Stephanie J
authors.initials: SJ
authors.lastname: Bissel
authors.affiliation: c Department of Pathology , University of Pittsburgh , Pittsburgh , PA , USA.
authors.forename: Clayton A
authors.initials: CA
authors.lastname: Wiley
authors.affiliation: a Center for Vaccines and Immunology, Department of Infectious Diseases, University of Georgia , Athens , GA USA.
authors.forename: Ted M
authors.initials: TM
authors.lastname: Ross
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood; D004195:Disease Models, Animal; D005260:Female; D007074:Immunoglobulin G / Q000097:blood; D007273:Injections, Intramuscular; D007444:Inulin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D008168:Lung / Q000473:pathology / Q000821:virology*; D008807:Mice, Inbred BALB C; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage; D018357:Respiratory Syncytial Virus Infections / Q000473:pathology*; D022261:Respiratory Syncytial Virus Vaccines / Q000008:administration & dosage / Q000276:immunology*; D012136:Respiratory Syncytial Viruses / Q000302:isolation & purification; D018417:Th1 Cells / Q000276:immunology*; D019562:Viral Load
chemical_list: D000276:Adjuvants, Immunologic; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; C408982:CPG-oligonucleotide; D007074:Immunoglobulin G; D009838:Oligodeoxyribonucleotides; D022261:Respiratory Syncytial Virus Vaccines; C576871:delta inulin; D007444:Inulin
keywords: F antigen; RSV; adjuvant; delta-inulin; mouse