Adult-like anti-mycobacterial T cell and in vivo dendritic cell responses following neonatal immunization with Ag85B-ESAT-6 in the IC31 adjuvant.
BACKGROUND
With the exception of some live vaccines, e.g. BCG, subunit vaccines formulated with "classical" adjuvants do not induce similar responses in neonates as in adults. The usual neonatal profile is characterized by lower levels of TH1-associated biomarkers. This has hampered the development of new neonatal vaccines for diseases that require early protection. Tuberculosis is one of the major targets for neonatal immunization. In this study, we assessed the immunogenicity of a novel candidate vaccine comprising a mycobacterial fusion protein, Ag85B-ESAT-6, in a neonatal murine immunization model.


RESULTS
The Ag85B-ESAT-6 fusion protein was formulated either with a classical alum based adjuvant or with the novel IC31 adjuvant. Following neonatal or adult immunization, 3 parameters were studied in vivo: (1) CD4(+) T cell responses, (2) vaccine targeting/activation of dendritic cells (DC) and (3) protection in a surrogate mycobacterial challenge model. Conversely to Alum, IC31 induced in both age groups strong Th1 and Th17 responses, characterized by multifunctional T cells expressing IL-2 and TNF-alpha with or without IFN-gamma. In the draining lymph nodes, a similarly small number of DC contained the adjuvant and/or the antigen following neonatal or adult immunization. Expression of CD40, CD80, CD86 and IL-12p40 production was focused on the minute adjuvant-bearing DC population. Again, DC targeting/activation was similar in adults and neonates. These DC/T cell responses resulted in an equivalent reduction of bacterial growth following infection with M. bovis BCG, whereas no protection was observed when Alum was used as adjuvant.


CONCLUSIONS
Neonatal immunization with the IC31-adjuvanted Ag85B-ESAT-6 subunit vaccine elicited adult-like multifunctional protective anti-mycobacterial T cell responses through the induction of an adult pattern of in vivo DC activation.
Kamath
Arun T
AT
World Health Organization Collaborating Center for Vaccinology and Neonatal Immunology, Department of Pathology-Immunology and Pediatrics, University of Geneva, Geneva, Switzerland.
Rochat
Anne-Françoise
AF
Valenti
Mario P
MP
Agger
Else Marie
EM
Lingnau
Karen
K
Andersen
Peter
P
Lambert
Paul-Henri
PH
Siegrist
Claire-Anne
CA
D000276:Adjuvants, Immunologic / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D000942:Antigens, Bacterial / Q000276:immunology*; D001426:Bacterial Proteins / Q000276:immunology*; D001428:Bacterial Vaccines / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D014376:Tuberculosis / Q000517:prevention & control
D000276:Adjuvants, Immunologic; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D001428:Bacterial Vaccines; C093276:ESAT-6 protein, Mycobacterium tuberculosis; D011993:Recombinant Fusion Proteins; C065036:antigen 85, Mycobacterium bovis