Immunization with heat-killed Mycobacterium bovis bacille Calmette–Guerin (BCG) in Eurocine™ L3 adjuvant protects against tuberculosis

• Published in: Vaccine 2004-03, Vol.22 (11), p.1498-1508
• Main Authors: Haile, M, Schröder, U, Hamasur, B, Pawlowski, A, Jaxmar, T, Källenius, G, Svenson, S.B
• Format: Article
• Language: English
• Subjects: Adjuvants, Immunologic; Administration, Intranasal; Animals; Applied microbiology; Bacterial diseases; BCG; BCG Vaccine - administration & dosage; BCG Vaccine - immunology; Biological and medical sciences; Body Weight; Chemistry, Pharmaceutical; Drug Delivery Systems; Emulsions; Eurocine L3; Female; Fundamental and applied biological sciences. Psychology; Human bacterial diseases; Immunization, Secondary; Immunoglobulin G - biosynthesis; Infectious diseases; Injections, Subcutaneous; Interferon-gamma - biosynthesis; Medical sciences; Medicin och hälsovetenskap; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Microbiology; Mycobacterium bovis; Survival Analysis; Tuberculosis; Tuberculosis - prevention & control; Tuberculosis and atypical mycobacterial infections; Vaccine; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects); Vaccines, Inactivated - immunology
• ISSN: 0264-410X; 1873-2518
• DOI: 10.1016/j.vaccine.2003.10.016

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™ 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™ 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™ 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™ 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™ L3 adjuvant elicited mycobacterial antigen-specific serum IgG and IFNγ responses. In general, among the different vaccine formulation(s) in the Eurocine™ L3 adjuvant those that produced a relatively high Th2 response, as measured by IgG1/IgG2a ratio and IFNγ production in vitro, were the most protective. In conclusion, H-kBCG in Eurocine™ L3 adjuvant could represent a safe and a more stable alternative to the conventional live BCG vaccine.