Enhanced immunogenicity of the tuberculosis subunit Rv0572c vaccine delivered in DMT liposome adjuvant as a BCG-booster

Lirong Mao; Lifa Xu; Xiaochun Wang; Yingru Xing; Jian Wang; Yanpeng Zhang; Wei Yuan; Jianpeng Du; Zilun Shi; Jilei Ma; Jingyan Zhang; Xiaohan Zhang; Xinping Wang

doi:10.1016/j.tube.2022.102186

Enhanced immunogenicity of the tuberculosis subunit Rv0572c vaccine delivered in DMT liposome adjuvant as a BCG-booster

Tuberculosis (Edinb). 2022 May:134:102186. doi: 10.1016/j.tube.2022.102186. Epub 2022 Feb 26.

Authors

Lirong Mao¹, Lifa Xu², Xiaochun Wang³, Yingru Xing⁴, Jian Wang⁵, Yanpeng Zhang⁵, Wei Yuan¹, Jianpeng Du⁵, Zilun Shi⁶, Jilei Ma⁷, Jingyan Zhang⁸, Xiaohan Zhang⁵, Xinping Wang¹

Affiliations

¹ Department of Immunology, School of Medicine, Anhui University of Science and Technology, Huainan, 232001, China.
² Department of Immunology, School of Medicine, Anhui University of Science and Technology, Huainan, 232001, China. Electronic address: ahhnlfxu@126.com.
³ Department of Pathogen Biology, School of Medicine, Anhui University of Science and Technology, Huainan, 232001, China. Electronic address: wxcvieri@126.com.
⁴ Department of Immunology, School of Medicine, Anhui University of Science and Technology, Huainan, 232001, China; Department of Clinical Laboratory, Anhui Zhongke Gengjiu Hospital, Hefei, 230000, China.
⁵ Department of Pathogen Biology, School of Medicine, Anhui University of Science and Technology, Huainan, 232001, China.
⁶ Department of Clinical Laboratory, Affiliated Cancer Hospital, Anhui University of Science and Technology, Huainan, 232001, China.
⁷ Department of Clinical Laboratory, The First Affiliated Hospital, Zhengzhou University, Zhengzhou, 450000, China.
⁸ Department of Clinical Laboratory, Affiliated Heping Hospital, Changzhi Medical College, Changzhi, 046000, China.

Abstract

COVID-19 has affected the progress made in the prevention and treatment of tuberculosis (TB); hence, the mortality of tuberculosis has risen. Different strategies-based novel TB vaccine candidates have been developed. This study identifies strategies to overcome the limitations of Bacille Calmette-Guérin (BCG) in preventing latent infection and reactivation of TB. The latency antigen Rv0572c was selected based on the mechanism of interaction between Mycobacterium tuberculosis and its host. The rRv0572c protein was used to stimulate whole blood samples derived from patients with clinically diagnosed active TB (ATBs) or latent TB infections (LTBIs) and healthy control (HCs) donors, confirming that this protein can be recognized by T cells in patients with TB, especially LTBIs. C57BL/6 mice were used to investigate the immunogenicity of the rRv0572c protein emulsified in the liposome adjuvant dimethyldioctadecylammonium [DDA], monophosphoryl lipid A [MPLA], trehalose-6, 6'-dibehenate [TDB] (DMT). The results demonstrated that rRv0572c/DMT could boost BCG-primed mice to induce antigen-specific CD4⁺ T cell production and generate functional T cells dominated by antigen-specific CD8⁺ T cells. The rRv0572c/DMT vaccine could also trigger limited Th2 humoral immune responses. These findings suggest that rRv0572c/DMT is a potential subunit vaccine candidate that can be used as a booster vaccine for BCG.

Keywords: Adjuvant; DosR protein; Liposome; Subunit vaccine; Tuberculosis.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adjuvants, Immunologic
Animals
Antigens, Bacterial
BCG Vaccine
CD8-Positive T-Lymphocytes
COVID-19*
Humans
Latent Tuberculosis*
Liposomes
Mice
Mice, Inbred C57BL
Mycobacterium tuberculosis*
Tuberculosis Vaccines*
Tuberculosis* / prevention & control
Vaccines, Subunit

Substances

Adjuvants, Immunologic
Antigens, Bacterial
BCG Vaccine
Liposomes
Tuberculosis Vaccines
Vaccines, Subunit