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.
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.
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
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