title: A liposome-based mycobacterial vaccine induces potent adult and neonatal multifunctional T cells through the exquisite targeting of dendritic cells.
abstract: BACKGROUND
  In the search for more potent and safer tuberculosis vaccines, CAF01 was identified as a remarkable formulation. Based on cationic liposomes and including a synthetic mycobacterial glycolipid as TLR-independent immunomodulator, it induces strong and protective T helper-1 and T helper-17 adult murine responses to Ag85B-ESAT-6, a major mycobacterial fusion protein. Here, we assessed whether these properties extend to early life and how CAF01 mediates its adjuvant properties in vivo.
  
  
  RESULTS
  Following adult or neonatal murine immunization, Ag85B-ESAT-6/CAF01 similarly reduced the post-challenge bacterial growth of M. bovis BCG, whereas no protection was observed using Alum as control. This protection was mediated by the induction of similarly strong Th1 and Th17 responses in both age groups. Multifunctional Th1 cells were already elicited after a single vaccine dose and persisted at high levels for at least 6 months even after neonatal priming. Unexpectedly, this potent adjuvanticity was not mediated by a massive targeting/activation of dendritic cells: in contrast, very few DCs in the draining lymph nodes were bearing the labeled antigen/adjuvant. The increased expression of the CD40 and CD86 activation markers was restricted to the minute portion of adjuvant-bearing DCs. However, vaccine-associated activated DCs were recovered several days after immunization.
  
  
  CONCLUSIONS
  The potent adult and neonatal adjuvanticity of CAF01 is associated in vivo with an exquisite but prolonged DC uptake and activation, fulfilling the preclinical requirements for novel tuberculosis vaccines to be used in early life.
authors.affiliation: World Health Organization Collaborating Center for Vaccinology and Neonatal Immunology, Department of Pathology-Immunology and Pediatrics, Medical Faculty of the University of Geneva, Geneva, Switzerland.
authors.forename: Arun T
authors.initials: AT
authors.lastname: Kamath
authors.forename: Anne-Françoise
authors.initials: AF
authors.lastname: Rochat
authors.forename: Dennis
authors.initials: D
authors.lastname: Christensen
authors.forename: Else Marie
authors.initials: EM
authors.lastname: Agger
authors.forename: Peter
authors.initials: P
authors.lastname: Andersen
authors.forename: Paul-Henri
authors.initials: PH
authors.lastname: Lambert
authors.forename: Claire-Anne
authors.initials: CA
authors.lastname: Siegrist
mesh_terms: D000276:Adjuvants, Immunologic; D000818:Animals; D051940:B7-2 Antigen / Q000096:biosynthesis; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D019013:CD40 Antigens / Q000096:biosynthesis; D002412:Cations; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism*; D008081:Liposomes / Q000737:chemistry*; D008198:Lymph Nodes / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009163:Mycobacterium bovis / Q000276:immunology* / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D032581:Tuberculosis Vaccines / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D051940:B7-2 Antigen; D019013:CD40 Antigens; D002412:Cations; D008081:Liposomes; D032581:Tuberculosis Vaccines