A liposome-based mycobacterial vaccine induces potent adult and neonatal multifunctional T cells through the exquisite targeting of dendritic cells.
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.
Kamath
Arun T
AT
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.
Rochat
Anne-Françoise
AF
Christensen
Dennis
D
Agger
Else Marie
EM
Andersen
Peter
P
Lambert
Paul-Henri
PH
Siegrist
Claire-Anne
CA
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*
D000276:Adjuvants, Immunologic; D051940:B7-2 Antigen; D019013:CD40 Antigens; D002412:Cations; D008081:Liposomes; D032581:Tuberculosis Vaccines