VALIDATE Seminar: Development of recombinant BCG Vaccine for tuberculosis utilizing Major Membrane Protein-II (MMP-II) antigen

VALIDATE is a network of vaccine researchers hosted by The University of Oxford.

About the Seminar:

A talk followed by a Q&A

An Introduction from Prof Manabu Ato and a talk from Dr Yumiko Tsukamoto

The End TB Strategy adopted by WHO aims to reduce 80% of tuberculosis incidents by year 2030. To achieve this goal, an efficient vaccine against tuberculosis will be required. Mycobacterium bovis BCG (BCG) has been the only vaccine against tuberculosis. While BCG prevents disseminated tuberculosis in childhood quite effectively, it is speculated the vaccine efficacy against adult pulmonary tuberculosis is relatively low. Further improvement of BCG will be necessary to reduce tuberculosis.

In this talk, Dr Tsukamoto will discuss her work at the Department of Mycobacteriology at the NIID, which identified Major Membrane Protein-II (MMP-II) antigen from Mycobacterium leprae. MMP-II is highly immunogenic and efficiently stimulates T cells to produce IFN-g in vitro. Mycobacterium tuberculosis (Mtb) expresses homolog of MMP-II antigen and the homology is 86% at amino acid level. This research has confirmed that MTB-derived MMP-II is also highly immunogenic and promotes IFN-g production in vitro.

This innovative approach has led to the development of a new recombinant BCG vaccine secreting Mtb-derived MMP-II and a further modified the BCG by depleting UreC gene in host BCG to induce phagosome-lysosome fusion in host cells infected with the recombinant BCG. They tested the resultant recombinant BCG in mouse model and it inhibited the multiplication of M. tuberculosis in mouse lungs more efficiently than host BCG and also succeeded to develop antibiotics-free recombinant BCG utilizing auxotrophy based recombination technique.

The study indicates that the recombinant BCG is the hopeful candidate vaccine against tuberculosis. As MMP-II is the common antigen between MTB and M. leprae, this recombinant BCG can be used as common vaccine against both tuberculosis and leprosy.