Abstract

The current live attenuated vaccine against tuberculosis, BCG, poses a risk of disseminated infections in immunocompromized subjects. Therefore, in this study we compared the protective effect of a heat-killed bacille Calmette-Guerin (H-kBCG) vaccine given in a new adjuvant (Eurocine(TM) L3) with the protection provided by the conventional live attenuated BCG vaccine in mice (C57BL/6 and BALB/c) challenged with virulent Mycobacterium tuberculosis (strain Harlingen). The H-kBCG vaccine alone, in accordance with earlier studies, did not give any or only gave slight protection compared to sham-vaccinated controls. However, the same vaccine given with Eurocine(TM) L3 adjuvant, either formulated as a suspension or as an emulsion, afforded significant levels of protection. This protection was at least as good as that of the control live attenuated BCG vaccine. The Eurocine(TM) L3 adjuvant is approved for human use as a nasal vaccine adjuvant and a successful phase I trial with nasal immunization with diphtheria vaccine has recently been performed in Sweden. Here we show that, in mice, intranasal priming with H-kBCG in Eurocine(TM) L3 adjuvant followed by intranasal booster resulted in the same level of protection as subcutaneous priming followed by intranasal booster. All H-kBCG formulations in the Eurocine(TM) L3 adjuvant elicited mycobacterial antigen-specific serum IgG and IFNgamma responses. In general, among the different vaccine formulation(s) in the Eurocine(TM) L3 adjuvant those that produced a relatively high Th2 response, as measured by IgGI/IgG2a ratio and IFNgamma production in vitro, were the most protective. In conclusion, H-kBCG in Eurocine(TM) L3 adjuvant could represent a safe and a more stable alternative to the conventional live BCG vaccine. (C) 2003 Elsevier Ltd. All rights reserved

Published in

Vaccine
2004, Volume: 22, number: 11-12, pages: 1498-1508
Publisher: ELSEVIER SCI LTD

Publication identifier

DOI: https://doi.org/10.1016/j.vacinne.2003.10.016

Permanent link to this page (URI)

https://res.slu.se/id/publ/4254