A VLP-Based Vaccine Displaying HBHA and MTP Antigens of Mycobacterium tuberculosis Induces Protective Immune Responses in M. tuberculosis H37Ra Infected Mice

Juan Wang; Tao Xie; Inayat Ullah; Youjun Mi; Xiaoping Li; Yang Gong; Pu He; Yuqi Liu; Fei Li; Jixi Li; Zengjun Lu; Bingdong Zhu

doi:10.3390/vaccines11050941

A VLP-Based Vaccine Displaying HBHA and MTP Antigens of Mycobacterium tuberculosis Induces Protective Immune Responses in M. tuberculosis H37Ra Infected Mice

Vaccines (Basel). 2023 May 4;11(5):941. doi: 10.3390/vaccines11050941.

Authors

Juan Wang¹, Tao Xie¹, Inayat Ullah¹, Youjun Mi^{1

2}, Xiaoping Li³, Yang Gong¹, Pu He¹, Yuqi Liu¹, Fei Li¹, Jixi Li⁴, Zengjun Lu^{5

6}, Bingdong Zhu^{1

6}

Affiliations

¹ Gansu Provincial Key Laboratory of Evidence Based Medicine and Clinical Translation, Lanzhou Center for Tuberculosis Research, Institute of Pathogen Biology, School of Basic Medical Sciences, Lanzhou University, Lanzhou 730000, China.
² Institute of Pathogenic Physiology, School of Basic Medical Sciences, Lanzhou University, Lanzhou 730000, China.
³ Respiratory Department of Lanzhou Pulmonary Hospital, Lanzhou 730000, China.
⁴ State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai 200438, China.
⁵ Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou 730000, China.
⁶ State Key Laboratory for Animal Disease Control and Prevention, College of Veterinary Medicine, Lanzhou University, Lanzhou 730000, China.

Abstract

Heparin-binding hemagglutinin (HBHA) and M. tuberculosis pili (MTP) are important antigens on the surface of Mycobacterium tuberculosis. To display these antigens effectively, the fusion protein HBHA-MTP with a molecular weight of 20 kD (L20) was inserted into the receptor-binding hemagglutinin (HA) fragment of influenza virus and was expressed along with matrix protein M1 in Sf9 insect cells to generate influenza virus-like particles (LV20 in short). The results showed that the insertion of L20 into the envelope of the influenza virus did not affect the self-assembly and morphology of LV20 VLPs. The expression of L20 was successfully verified by transmission electron microscopy. Importantly, it did not interfere with the immunogenicity reactivity of LV20 VLPs. We demonstrated that LV20 combined with the adjuvant composed of DDA and Poly I: C (DP) elicited significantly higher antigen-specific antibodies and CD4⁺/CD8⁺ T cell responses than PBS and BCG vaccination in mice. It suggests that the insect cell expression system is an excellent protein production system, and LV20 VLPs could be a novel tuberculosis vaccine candidate for further evaluation.

Keywords: Heparin-binding hemagglutinin; Mycobacterium tuberculosis; Mycobacterium tuberculosis pili; subunit vaccine; virus-like particles.

Grants and funding

The work was funded by the National Key Research and Development Program of China (2021YFC2301503), the Gansu Science and Technology Project in China (21JR7RA534, 21JR7RA443), and a program from the State Key Laboratory of Veterinary Etiological Biology of China (SKLVEB2020KFKT009).