In vivo electroporation of a codon-optimized BERopt DNA vaccine protects mice from pathogenic Mycobacterium tuberculosis aerosol challenge

Jiansong Tang; Yi Cai; Jianguo Liang; Zhiwu Tan; Xian Tang; Chi Zhang; Lin Cheng; Jingying Zhou; Haibo Wang; Wing-Cheong Yam; Xinchun Chen; Hui Wang; Zhiwei Chen

doi:10.1016/j.tube.2018.07.003

In vivo electroporation of a codon-optimized BER^opt DNA vaccine protects mice from pathogenic Mycobacterium tuberculosis aerosol challenge

Tuberculosis (Edinb). 2018 Dec:113:65-75. doi: 10.1016/j.tube.2018.07.003. Epub 2018 Jul 10.

Authors

Jiansong Tang¹, Yi Cai², Jianguo Liang³, Zhiwu Tan³, Xian Tang², Chi Zhang², Lin Cheng³, Jingying Zhou³, Haibo Wang³, Wing-Cheong Yam⁴, Xinchun Chen², Hui Wang⁵, Zhiwei Chen⁶

Affiliations

¹ AIDS Institute and Department of Microbiology, State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Li Ka Shing Faculty of Medicine, Hong Kong SAR, PR China; HKU AIDS Institute Shenzhen Research Laboratory and Guangdong Key Laboratory for Emerging Infectious Disease, Shenzhen Third People's Hospital, Guangdong Medical College, Shenzhen, PR China.
² HKU AIDS Institute Shenzhen Research Laboratory and Guangdong Key Laboratory for Emerging Infectious Disease, Shenzhen Third People's Hospital, Guangdong Medical College, Shenzhen, PR China.
³ AIDS Institute and Department of Microbiology, State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Li Ka Shing Faculty of Medicine, Hong Kong SAR, PR China.
⁴ Department of Microbiology, Queen Mary Hospital, The University of Hong Kong, Hong Kong SAR, PR China.
⁵ HKU AIDS Institute Shenzhen Research Laboratory and Guangdong Key Laboratory for Emerging Infectious Disease, Shenzhen Third People's Hospital, Guangdong Medical College, Shenzhen, PR China. Electronic address: [email protected].
⁶ AIDS Institute and Department of Microbiology, State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Li Ka Shing Faculty of Medicine, Hong Kong SAR, PR China; HKU AIDS Institute Shenzhen Research Laboratory and Guangdong Key Laboratory for Emerging Infectious Disease, Shenzhen Third People's Hospital, Guangdong Medical College, Shenzhen, PR China. Electronic address: [email protected].

PMID: 30514515
DOI: 10.1016/j.tube.2018.07.003

Abstract

DNA vaccines have been extensively studied as preventative and therapeutic interventions for various infectious diseases such as tuberculosis, HIV/AIDS and influenza. Despite promising progresses made, improving the immunogenicity of DNA vaccine remains a technical challenge for clinical development. In this study, we investigated a tuberculosis DNA vaccine BER^opt, which contained a codon-optimized fusion immunogen Ag85B-ESAT-6-Rv2660c for enhanced mammalian cell expression and immunogenicity. BER^opt immunization through in vivo electroporation in BALB/c mice induced surprisingly high frequencies of Ag85B tetramer⁺ CD8⁺ T cells in peripheral blood and IFN-γ-secreting CD8⁺ T cells in splenocytes. Meanwhile, the BER^opt vaccine-induced long-lasting T cell immunity protected BALB/c mice from high dose viral challenge using a modified vaccinia virus Tiantan strain expressing mature Ag85B protein (MVTT-m85B) and the virulent M. tb H37Rv aerosol challenge. Since the BER^opt DNA vaccine does not induce anti-vector immunity, the strong immunogenicity and protective efficacy of this novel DNA vaccine warrant its future development for M. tb prevention and immunotherapy to alleviate the global TB burden.

Keywords: BCG; BER(opt); DNA vaccine; Mycobacterium tuberculosis; Tuberculosis.

Publication types

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

MeSH terms

Acyltransferases / administration & dosage*
Acyltransferases / genetics
Acyltransferases / immunology
Aerosols
Animals
Antigens, Bacterial / administration & dosage*
Antigens, Bacterial / genetics
Antigens, Bacterial / immunology
Bacterial Proteins / administration & dosage*
Bacterial Proteins / genetics
Bacterial Proteins / immunology
CD8-Positive T-Lymphocytes / immunology
CD8-Positive T-Lymphocytes / microbiology
Cells, Cultured
Codon
Disease Models, Animal
Electrochemotherapy / methods*
Female
Immunization
Immunogenicity, Vaccine*
Inhalation Exposure
Interferon-gamma / immunology
Mice, Inbred BALB C
Mycobacterium tuberculosis / genetics
Mycobacterium tuberculosis / immunology
Mycobacterium tuberculosis / pathogenicity*
Spleen / immunology
Spleen / microbiology
Time Factors
Tuberculosis Vaccines / administration & dosage*
Tuberculosis Vaccines / genetics
Tuberculosis Vaccines / immunology
Tuberculosis, Pulmonary / immunology
Tuberculosis, Pulmonary / microbiology
Tuberculosis, Pulmonary / prevention & control*
Vaccines, DNA / administration & dosage
Vaccinia virus / genetics
Vaccinia virus / immunology

Substances

Aerosols
Antigens, Bacterial
Bacterial Proteins
Codon
ESAT-6 protein, Mycobacterium tuberculosis
IFNG protein, mouse
Rv2660c protein, Mycobacterium tuberculosis
Tuberculosis Vaccines
Vaccines, DNA
Interferon-gamma
Acyltransferases
antigen 85B, Mycobacterium tuberculosis