title: Enhanced immunogenicity of a respiratory syncytial virus (RSV) F subunit vaccine formulated with the adjuvant GLA-SE in cynomolgus macaques.
abstract: Respiratory syncytial virus (RSV) causes significant disease in elderly adults, but an effective vaccine is not yet available. We have previously reported that vaccines consisting of engineered respiratory syncytial virus soluble fusion protein (RSV sF) adjuvanted with glucopyranosyl lipid A (GLA) in an oil-in-water emulsion (stable emulsion [SE]) induce RSV F-specific T and B cell responses in mice and rats that protect from viral challenge. Here, we evaluated the immunogenicity of GLA-SE adjuvanted RSV sF vs unadjuvanted RSV sF vaccines in cynomolgus macaques (Macaca fascicularis). RSV F-specific IgG, RSV neutralizing antibodies, and RSV F-specific T cell IFNγ ELISPOT responses induced by GLA-SE adjuvanted RSV sF peaked at week 6 at significantly higher levels than achieved by unadjuvanted RSV sF and remained detectable through week 24, demonstrating response longevity. Two weeks after a week 24 booster immunization, humoral and cellular responses reached levels similar to those seen at the earlier peak response. Importantly, the GLA-SE adjuvanted RSV sF vaccine induced cross-neutralizing antibodies to other RSV A and B strains as well as F-specific IgA and IgG memory B cells. GLA-SE adjuvanted RSV sF was also demonstrated to drive a Th1-biased response characterized by more IFNγ than IL-4. This study indicates that a GLA-SE adjuvanted RSV sF vaccine induces robust humoral and Th1-biased cellular immunity in non-human primates and may benefit human populations at risk for RSV disease.
authors.affiliation: Applied Immunology and Microbiology, Translational Sciences, MedImmune, 319 North Bernardo Avenue, Mountain View, CA 94043, USA.
authors.forename: Kathryn
authors.initials: K
authors.lastname: Patton
authors.affiliation: Applied Immunology and Microbiology, Translational Sciences, MedImmune, 319 North Bernardo Avenue, Mountain View, CA 94043, USA.
authors.forename: Shahin
authors.initials: S
authors.lastname: Aslam
authors.affiliation: Applied Immunology and Microbiology, Translational Sciences, MedImmune, 319 North Bernardo Avenue, Mountain View, CA 94043, USA.
authors.forename: Cindy
authors.initials: C
authors.lastname: Shambaugh
authors.affiliation: Applied Immunology and Microbiology, Translational Sciences, MedImmune, 319 North Bernardo Avenue, Mountain View, CA 94043, USA.
authors.forename: Rui
authors.initials: R
authors.lastname: Lin
authors.affiliation: Applied Immunology and Microbiology, Translational Sciences, MedImmune, 319 North Bernardo Avenue, Mountain View, CA 94043, USA.
authors.forename: Darren
authors.initials: D
authors.lastname: Heeke
authors.affiliation: Pathology, MedImmune, 319 North Bernardo Avenue, Mountain View, CA 94043, USA.
authors.forename: Chris
authors.initials: C
authors.lastname: Frantz
authors.affiliation: Applied Immunology and Microbiology, Translational Sciences, MedImmune, 319 North Bernardo Avenue, Mountain View, CA 94043, USA.
authors.forename: Fengrong
authors.initials: F
authors.lastname: Zuo
authors.affiliation: Translational Medicine, MedImmune, One Medimmune Way, Gaithersburg, MD 20878, USA.
authors.forename: Mark T
authors.initials: MT
authors.lastname: Esser
authors.affiliation: Applied Immunology and Microbiology, Translational Sciences, MedImmune, 319 North Bernardo Avenue, Mountain View, CA 94043, USA.
authors.forename: Xavier
authors.initials: X
authors.lastname: Paliard
authors.affiliation: Applied Immunology and Microbiology, Translational Sciences, MedImmune, 319 North Bernardo Avenue, Mountain View, CA 94043, USA. Electronic address: LambertS@medimmune.com.
authors.forename: Stacie L
authors.initials: SL
authors.lastname: Lambert
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood; D003429:Cross Reactions; D058501:Enzyme-Linked Immunospot Assay; D005960:Glucosides / Q000008:administration & dosage; D007070:Immunoglobulin A / Q000276:immunology; D007074:Immunoglobulin G / Q000097:blood; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000378:metabolism; D008050:Lipid A / Q000008:administration & dosage; D008252:Macaca fascicularis; D008297:Male; D022261:Respiratory Syncytial Virus Vaccines / Q000008:administration & dosage / Q000276:immunology*; D012136:Respiratory Syncytial Viruses / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D013997:Time Factors; D016896:Treatment Outcome; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D005960:Glucosides; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D008050:Lipid A; D022261:Respiratory Syncytial Virus Vaccines; D022223:Vaccines, Subunit; D007371:Interferon-gamma
keywords: Adjuvant; Non-human primates; RSV F; Vaccine