A VLP-Based Vaccine Displaying HBHA and MTP Antigens of <em>Mycobacterium tuberculosis</em> Induces Potentially Protective Immune Responses in <em>M. tuberculosis</em> 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
Affiliations
Juan Wang
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
Tao Xie
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
Inayat Ullah
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
Youjun Mi
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
Xiaoping Li
Respiratory Department of Lanzhou Pulmonary Hospital, Lanzhou 730000, China
Yang Gong
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
Pu He
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
Yuqi Liu
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
Fei Li
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
Jixi Li
State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai 200438, China
Zengjun Lu
Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou 730000, China
Bingdong Zhu
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
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, and reduced the bacterial load in the lungs of mice infected with M. tuberculosis H37Ra. 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.
