Recombinant mycobacterial DNA-binding protein 1 with post-translational modifications boosts IFN-gamma production from BCG-vaccinated individuals' blood cells in combination with CpG-DNA

• Published in: Scientific reports Vol. 14; no. 1; p. 9141
• Main Authors: Ozeki, Yuriko, Yokoyama, Akira, Nishiyama, Akihito, Yoshida, Yutaka, Ohara, Yukiko, Mashima, Tsukasa, Tomiyama, Chikako, Shaban, Amina K, Takeishi, Atsuki, Osada-Oka, Mayuko, Yamaguchi, Takehiro, Tateishi, Yoshitaka, Maeyama, Jun-Ichi, Hakamata, Mariko, Moro, Hiroshi, Kikuchi, Toshiaki, Hayashi, Daisuke, Suzuki, Fumiko, Yamamoto, Toshiko, Iho, Sumiko, Katahira, Masato, Yamamoto, Saburo, Matsumoto, Sohkichi
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 21.04.2024; Nature Publishing Group UK; Nature Portfolio
• Subjects: Antigens; Bacillus Calmette-Guerin vaccine; Bacterial Proteins - immunology; BCG; BCG Vaccine - immunology; Blood cells; CpG Islands; Deoxyribonucleic acid; DNA; DNA vaccines; DNA-binding protein; DNA-Binding Proteins - genetics; DNA-Binding Proteins - immunology; DNA-Binding Proteins - metabolism; E coli; Escherichia coli - genetics; Escherichia coli - metabolism; Female; Health risks; Humans; Immunogenicity; Interferon-gamma - metabolism; Mycobacterium smegmatis - immunology; Mycobacterium smegmatis - metabolism; Mycobacterium tuberculosis - immunology; Oligodeoxyribonucleotides - pharmacology; Peripheral blood; Post-translation; Protein Processing, Post-Translational; Proteins; Public health; Recombinant Proteins - immunology; Recombinants; Translation; Tuberculosis; Tuberculosis - immunology; Tuberculosis - prevention & control; Vaccine efficacy; Vaccines; γ-Interferon
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-024-58836-8

Tuberculosis remains a large health threat, despite the availability of the tuberculosis vaccine, BCG. As BCG efficacy gradually decreases from adolescence, BCG-Prime and antigen-booster may be an efficient strategy to confer vaccine efficacy. Mycobacterial DNA-binding protein 1 (MDP1, namely Rv2986c, hupB or HU) is a major Mycobacterium tuberculosis protein that induces vaccine-efficacy by co-administration with CpG DNA. To produce MDP1 for booster-vaccine use, we have created recombinant MDP1 produced in both Escherichia coli (eMDP1) and Mycolicibacterium smegmatis (mMDP1), an avirulent rapid-growing mycobacteria. We tested their immunogenicity by checking interferon (IFN)-gamma production by stimulated peripheral blood cells derived from BCG-vaccinated individuals. Similar to native M. tuberculosis MDP1, we observed that most lysin resides in the C-terminal half of mMDP1 are highly methylated. In contrast, eMDP1 had less post-translational modifications and IFN-gamma stimulation. mMDP1 stimulated the highest amount of IFN-gamma production among the examined native M. tuberculosis proteins including immunodominant MPT32 and Antigen 85 complex. MDP1-mediated IFN-gamma production was more strongly enhanced when combined with a new type of CpG DNA G9.1 than any other tested CpG DNAs. Taken together, these results suggest that the combination of mMDP1 and G9.1 possess high potential use for human booster vaccine against tuberculosis.