The Combined CTA1-DD/ISCOMs Vector Is an Effective Intranasal Adjuvant for Boosting PriorMycobacterium bovisBCG Immunity toMycobacterium tuberculosis

• DOI: 10.1128/iai.01290-06
• Publication Date: 2006-12-20T23:51:25Z
• Authors: Claire Swetman An...; Jes Dietrich; Else Marie Agger; Nils Y. Lycke; Karin Lövgren; Peter Andersen
• Keywords: Antigens, Bacterial; Cholera Toxin; 0303 health sciences; Recombinant Fusion Proteins; Immunization, Secondary; Mycobacterium tuberculosis; Th1 Cells; Flow Cytometry; Mycobacterium bovis; Immunoglobulin A; 3. Good health; Mice, Inbred C57BL; Interferon-gamma; Mice; 03 medical and health sciences; Adjuvants, Immunologic; Bacterial Proteins; Animals; Female; Tuberculosis Vaccines; Administration, Intranasal; ISCOMs

ABSTRACTInfection withMycobacterium tuberculosis, the causative agent of tuberculosis (TB), remains one of the leading causes of mortality worldwide. The current “gold standard” vaccineMycobacterium bovisBCG 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 asM. 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.