Potential of Mycobacterium tuberculosis resuscitation-promoting factors as antigens in novel tuberculosis sub-unit vaccines

• Published in: Microbes and infection Vol. 14; no. 1; pp. 86 - 95
• Main Authors: Romano, M., Aryan, E., Korf, H., Bruffaerts, N., Franken, C.L.M.C., Ottenhoff, T.H.M., Huygen, K.
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier Masson SAS 2012; Elsevier
• Subjects: Animals; Antigens, Bacterial - genetics; Antigens, Bacterial - immunology; Applied microbiology; Bacterial Proteins - genetics; Bacterial Proteins - immunology; Bacteriology; BCG Vaccine - immunology; Biological and medical sciences; Cytokines - genetics; Cytokines - immunology; Epitopes - immunology; Female; Fundamental and applied biological sciences. Psychology; Human immunodeficiency virus; Humans; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Microbiology; Micrococcus luteus; Micrococcus luteus - genetics; Micrococcus luteus - immunology; Miscellaneous; Mycobacterium bovis; Mycobacterium bovis - genetics; Mycobacterium bovis - immunology; Mycobacterium tuberculosis; Mycobacterium tuberculosis - genetics; Mycobacterium tuberculosis - immunology; Resuscitation-promoting factor; Th1 Cells - immunology; Tuberculosis - immunology; Tuberculosis - pathology; Tuberculosis - prevention & control; Tuberculosis Vaccines - genetics; Tuberculosis Vaccines - immunology; Vaccine development; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects); Vaccines, DNA - genetics; Vaccines, DNA - immunology; Mycobacterium tuberculosis; Vaccine development; Resuscitation-promoting factor; Antigen; Mycobacteriales; Mycobacteriaceae; Bacteria; Actinomycetes; Vaccine; Resuscitation
• ISSN: 1286-4579; 1769-714X
• DOI: 10.1016/j.micinf.2011.08.011

Novel vaccines are needed to control tuberculosis (TB), the bacterial infectious disease that together with malaria and HIV is worldwide responsible for high levels of morbidity and mortality. TB can result from the reactivation of an initially controlled latent infection by
Mycobacterium tuberculosis (
Mtb).
Mtb proteins for which a possible role in this reactivation process has been hypothesized are the five homologs of the resuscitation-promoting factor of
Micrococcus luteus, namely
Mtb Rv0867c (
rpfA), Rv1009 (
rpfB), Rv1884c (
rpfC), Rv2389c (
rpfD) and Rv2450c (
rpfE). Analysis of the immune recognition of these 5 proteins following
Mtb infection or
Mycobacterium bovis BCG vaccination of mice showed that Rv1009 (rpfB) and Rv2389c (rpfD) are the most antigenic in the tested models. We therefore selected rpfB and rpfD for testing their vaccine potential as plasmid DNA vaccines. Elevated cellular immune responses and modest but significant protection against intra-tracheal
Mtb challenge were induced by immunization with the
rpfB encoding DNA vaccine. The results indicate that rpfB is the most promising candidate of the five rpf-like proteins of
Mtb in terms of its immunogenicity and protective efficacy and warrants further analysis for inclusion as an antigen in novel TB vaccines.