title: TLR4 ligands augment antigen-specific CD8+ T lymphocyte responses elicited by a viral vaccine vector.
abstract: Toll-like receptor (TLR) ligands are critical activators of innate immunity and are being developed as vaccine adjuvants. However, their utility in conjunction with viral vector-based vaccines remains unclear. In this study, we evaluated the impact of a variety of TLR ligands on antigen-specific CD8(+) T lymphocyte responses elicited by a recombinant adenovirus serotype 26 (rAd26) vector expressing simian immunodeficiency virus Gag in mice. The TLR3 ligand poly(I:C) suppressed Gag-specific cellular immune responses, whereas the TLR4 ligands lipopolysaccharide and monophosphoryl lipid A substantially augmented the magnitude and functionality of these responses by a MyD88- and TRIF-dependent mechanism. These data demonstrate that TLR ligands can modulate the immunogenicity of viral vaccine vectors both positively and negatively. Moreover, these findings suggest the potential utility of TLR4 ligands as adjuvants for rAd vector-based vaccines.
authors.affiliation: Division of Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
authors.forename: Elizabeth G
authors.initials: EG
authors.lastname: Rhee
authors.forename: R Phelps
authors.initials: RP
authors.lastname: Kelley
authors.forename: Isha
authors.initials: I
authors.lastname: Agarwal
authors.forename: Diana M
authors.initials: DM
authors.lastname: Lynch
authors.forename: Annalena
authors.initials: A
authors.lastname: La Porte
authors.forename: Nathaniel L
authors.initials: NL
authors.lastname: Simmons
authors.forename: Sarah L
authors.initials: SL
authors.lastname: Clark
authors.forename: Dan H
authors.initials: DH
authors.lastname: Barouch
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D015750:Genes, gag; D005822:Genetic Vectors; D008024:Ligands; D008070:Lipopolysaccharides / Q000008:administration & dosage; D051379:Mice; D008810:Mice, Inbred C57BL; D011070:Poly I-C / Q000008:administration & dosage; D015302:Simian Immunodeficiency Virus / Q000235:genetics; D051197:Toll-Like Receptor 4 / Q000378:metabolism*; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D014765:Viral Vaccines / Q000008:administration & dosage / Q000235:genetics* / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D008024:Ligands; D008070:Lipopolysaccharides; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D014614:Vaccines, Synthetic; D014765:Viral Vaccines; D011070:Poly I-C