A new poly(I:C)-decorated PLGA-PEG nanoparticle promotes Mycobacterium tuberculosis fusion protein to induce comprehensive immune responses in mice intranasally

Xiufen Du; Daquan Tan; Yang Gong; Yifan Zhang; Jiangyuan Han; Wei Lv; Tao Xie; Pu He; Zongjie Hou; Kun Xu; Jiying Tan; Bingdong Zhu

doi:10.1016/j.micpath.2021.105335

A new poly(I:C)-decorated PLGA-PEG nanoparticle promotes Mycobacterium tuberculosis fusion protein to induce comprehensive immune responses in mice intranasally

Microb Pathog. 2022 Jan:162:105335. doi: 10.1016/j.micpath.2021.105335. Epub 2021 Nov 30.

Authors

Xiufen Du¹, Daquan Tan², Yang Gong², Yifan Zhang², Jiangyuan Han², Wei Lv², Tao Xie², Pu He¹, Zongjie Hou³, Kun Xu¹, Jiying Tan⁴, Bingdong Zhu⁵

Affiliations

¹ Gansu Provincial Key Laboratory of Evidence Based Medicine and Clinical Translation and Lanzhou Center for Tuberculosis Research, School of Basic Medical Sciences, Lanzhou University, Lanzhou, 730000, China; Department of Immunology, School of Basic Medical Sciences, Lanzhou University, Lanzhou, 730000, China.
² Gansu Provincial Key Laboratory of Evidence Based Medicine and Clinical Translation and Lanzhou Center for Tuberculosis Research, School of Basic Medical Sciences, Lanzhou University, Lanzhou, 730000, China; Institute of Pathogen Biology, School of Basic Medical Sciences, Lanzhou University, Lanzhou, 730000, China.
³ Department of Immunology, School of Basic Medical Sciences, Lanzhou University, Lanzhou, 730000, China.
⁴ Gansu Provincial Key Laboratory of Evidence Based Medicine and Clinical Translation and Lanzhou Center for Tuberculosis Research, School of Basic Medical Sciences, Lanzhou University, Lanzhou, 730000, China; Department of Immunology, School of Basic Medical Sciences, Lanzhou University, Lanzhou, 730000, China. Electronic address: tanjy@lzu.edu.cn.
⁵ Gansu Provincial Key Laboratory of Evidence Based Medicine and Clinical Translation and Lanzhou Center for Tuberculosis Research, School of Basic Medical Sciences, Lanzhou University, Lanzhou, 730000, China; Institute of Pathogen Biology, School of Basic Medical Sciences, Lanzhou University, Lanzhou, 730000, China. Electronic address: bdzhu@lzu.edu.cn.

PMID: 34861347
DOI: 10.1016/j.micpath.2021.105335

Abstract

Protein-based subunit vaccine against tuberculosis (TB) is regarded as safer but with lower immunogenicity. To investigate effective adjuvant to improve the immunogenicity of TB subunit vaccine, we modified ploy(I:C) onto PLGA-PEG copolymer nanoparticle with polydopamine to produce a new nanoparticle adjuvant named "PLGA-PEG-poly(I:C)" (NP). M. tuberculosis fusion proteins Mtb10.4-HspX and ESAT-6-Rv2626c (M4) were encapsulated in the nanoparticles to produce the NP/M4 subunit vaccine. The PLGA-PEG/M4 nanoparticle was 200.21 ± 1.07 nm in diameter, and the polydispersity index (PDI) was 0.127 ± 0.02. Following modification with poly(I:C) by polydopamine, the NP/M4 was administered to C57BL/6 female mice intranasally and the immune responses were evaluated. The NP/M4 significantly induced antigen-specific CD4⁺ T cells proliferation, IL-2 and IFN-γ production. In addition, the NP/M4 could promote the production of antigen-specific IgG, IgG1, IgG2c in serum, and sIgA in lung washings. Overall, our results indicated that the NP would be a potential TB subunit vaccine adjuvant with the ability to induce strong Th1-type cell-mediated immunity and humoral immune responses.

Keywords: Adjuvant; Mycobacterium tuberculosis; PLGA copolymer nanoparticle; Poly(I:C); Subunit vaccine.

MeSH terms

Adjuvants, Immunologic
Adjuvants, Vaccine
Animals
Antigens, Bacterial
Female
Immunity, Humoral
Mice
Mice, Inbred C57BL
Mycobacterium tuberculosis*
Nanoparticles*

Substances

Adjuvants, Immunologic
Adjuvants, Vaccine
Antigens, Bacterial