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

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

About the Seminar: A talk followed by a Q&A

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

The WHO has adopted the End TB Strategy, which aimed to reduce 80% of tuberculosis cases by the year 2030. To achieve this objective, the development of an effective tuberculosis vaccine becomes crucial. Historically, the Mycobacterium bovis BCG (BCG) vaccine has been the primary defense against tuberculosis. While BCG has proven to be highly effective in preventing disseminated tuberculosis in children, its efficacy in preventing adult pulmonary tuberculosis is believed to be relatively low. Thus, further advancements and enhancements of the BCG vaccine are necessary to combat tuberculosis.

During this presentation, Dr. Tsukamoto discussed her research conducted at the Department of Mycobacteriology at the NIID. The focus of her work was the identification of the Major Membrane Protein-II (MMP-II) antigen derived from Mycobacterium leprae. MMP-II demonstrated high immunogenicity and effectively stimulated T cells to produce IFN-g in laboratory settings. Interestingly, Mycobacterium tuberculosis (Mtb) also expresses a homologous antigen to MMP-II, with an 86% amino acid level similarity. This research confirmed that MMP-II derived from Mtb is also highly immunogenic and induces IFN-g production in vitro.

The innovative approach led to the development of a novel recombinant BCG vaccine that secretes MMP-II derived from Mtb. Additionally, the BCG vaccine was further modified by depleting the UreC gene within host BCG cells. This modification aimed to induce phagosome-lysosome fusion in host cells infected with the recombinant BCG. The resulting recombinant BCG was tested in a mouse model and exhibited more efficient inhibition of M. tuberculosis multiplication in the lungs compared to the host BCG. Moreover, the researchers successfully developed an antibiotics-free recombinant BCG utilizing an auxotrophy-based recombination technique.

This study indicates that the recombinant BCG vaccine holds promise as a potential candidate for preventing tuberculosis. Since MMP-II is a shared antigen between MTB and M. leprae, this recombinant BCG vaccine could be used as a common preventive measure against both tuberculosis and leprosy.


About the Speakers

Yumiko Tsukamoto

Dr Yumiko Tsukamoto is Senior Research Scientist at the Department of Mycobacteriology, Leprosy Research Center, National Institute of Infectious Diseases, Japan. As a member of a research team focused on immunological research and vaccine development against Mycobacterium leprae and Mycobacterium tuberculosis (Mtb) for over a decade, Yumiko has extensive experience in analyzing vaccine efficacy using mouse models, conducting bacteriological analyses of BCG, and implementing immunological techniques.

Manabu Ato

Prof Manabu Ato is Director of Mycobacteriology, Leprosy Research Centre, National Institute of Infectious Diseases since 2017. Manabu joined NIID as a Researcher in 2004, and was appointed as Director, Department of Immunology in 2013.

Manabu's research covers a diverse area within infectious diseases, including leprosy, new TB vaccine, non-tuberculous mycobacterial diseases, melioidosis, and intracellular pathogens.