The combined CTA1-DD/ISCOMs vector is an effective intranasal adjuvant for boosting prior Mycobacterium bovis BCG immunity to Mycobacterium tuberculosis.
Infection with Mycobacterium tuberculosis, the causative agent of tuberculosis (TB), remains one of the leading causes of mortality worldwide. The current "gold standard" vaccine Mycobacterium bovis BCG has a limited efficacy that wanes over time. The development of a vaccine to boost BCG-induced immunity is therefore a highly active area of research. Mucosal administration of vaccines is believed to provide better protection against pathogens, such as M. tuberculosis, that invade the host via mucosal surfaces. In this study we demonstrate that an intranasal vaccine, comprising the antigenic fusion protein Ag85B-ESAT-6 and the mucosal combined adjuvant vector CTA1-DD/ISCOMs, strongly promotes a Th1-specific immune response, dominated by gamma interferon-secreting CD4-positive T cells. Mucosal administration of Ag85B-ESAT-6 mixed with CTA1-DD/ISCOMs strongly boosted prior BCG immunity, leading to a highly increased recruitment of antigen-specific cells to the site of infection. Most importantly, we observed a significantly (P < 0.001) reduced bacterial burden in the lung compared to nonboosted control animals. Thus, the results demonstrate the effectiveness of mucosal vaccination with Ag85B-ESAT-6 mixed with CTA1-DD/ISCOMs as adjuvant for stimulating TB-specific protective immunity in the lung.
Andersen
Claire Swetman
CS
Staten Serum Institute, TB Vaccine Research, Department of Infectious Disease Immunology, 5 Artillerivej, DK-2300 Copenhagen S, Denmark.
Dietrich
Jes
J
Agger
Else Marie
EM
Lycke
Nils Y
NY
Lövgren
Karin
K
Andersen
Peter
P
D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000281:Administration, Intranasal; D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology; D001426:Bacterial Proteins / Q000276:immunology; D002772:Cholera Toxin / Q000008:administration & dosage / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D016882:ISCOMs / Q000008:administration & dosage / Q000276:immunology*; D007117:Immunization, Secondary / Q000379:methods; D007070:Immunoglobulin A / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D009163:Mycobacterium bovis / Q000276:immunology*; D009169:Mycobacterium tuberculosis / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D032581:Tuberculosis Vaccines / Q000276:immunology*
D000276:Adjuvants, Immunologic; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; C440610:CTA1-DD protein, recombinant; D016882:ISCOMs; D007070:Immunoglobulin A; D011993:Recombinant Fusion Proteins; D032581:Tuberculosis Vaccines; D007371:Interferon-gamma; D002772:Cholera Toxin