title: Adjuvants recognized by toll-like receptors inhibit the induction of polarized type 2 T cell responses by natural attachment (G) protein of respiratory syncytial virus.
abstract: Immunization with native fusion (F) protein from respiratory syncytial virus (RSV) adsorbed to alum adjuvant generates greater than fourfold rises in serum neutralizing antibody titers in approximately 50% of seropositive humans. Using BALB/c mice we demonstrate herein that enhanced neutralization titers and accelerated clearance of virus from the lungs after challenge are possible if the attachment (G) glycoprotein is added to F protein-based vaccines. We further reveal for the first time that polarized type 2 T cell responses and immunopathology associated with G protein are inhibited by adjuvants recognized by toll-like receptors (TLR). Co-formulation with compounds that targeted TLR-2, TLR-3, TLR-4, or TLR-9 elicited significantly diminished type 2 T cell responses that caused granulocytic inflammation and eosinophilia in the airways after challenge. These results were not observed with recombinant IL-12 or QS-21. The data are important for improving combination vaccines for RSV.
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D018899:CpG Islands / Q000235:genetics; D016207:Cytokines / Q000096:biosynthesis; D004804:Eosinophils / Q000473:pathology; D005260:Female; D005434:Flow Cytometry; D006098:Granulocytes / Q000473:pathology; D007371:Interferon-gamma / Q000502:physiology; D018664:Interleukin-12 / Q000502:physiology; D008168:Lung / Q000473:pathology; D008562:Membrane Glycoproteins / Q000187:drug effects* / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D010641:Phenotype; D011956:Receptors, Cell Surface / Q000187:drug effects* / Q000276:immunology; D018113:Respiratory Syncytial Virus, Human / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D013926:Thrombopoietin; D051195:Toll-Like Receptor 2; D051196:Toll-Like Receptor 3; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D014759:Viral Envelope Proteins / Q000276:immunology*; D010948:Viral Plaque Assay
chemical_list: D000276:Adjuvants, Immunologic; D016207:Cytokines; C066028:G protein, Bovine respiratory syncytial virus; D008562:Membrane Glycoproteins; D011956:Receptors, Cell Surface; D051195:Toll-Like Receptor 2; D051196:Toll-Like Receptor 3; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D014759:Viral Envelope Proteins; D018664:Interleukin-12; D007371:Interferon-gamma; D013926:Thrombopoietin