A novel dendritic cell-targeted lentiviral vector, encoding Ag85A-ESAT6 fusion gene of Mycobacterium tuberculosis, could elicit potent cell-mediated immune responses in mice.
Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis (Mtb), leading to high mortality worldwide. It is well-established that cellular immunity plays a critical role to control Mtb infection. Dendritic Cells (DCs) are potent antigen presenting cells, which play an important role to prime cell-mediated immune responses. In vivo targeting of DCs has been shown to induce both strong cellular immunity and protection against tumor challenges. The aim of the present study was not only to assess the immunizing potential of a novel DC-targeted recombinant lentivirus expressing fusion antigen Ag85A-ESAT6 of Mtb, but also to compare it with a recombinant lentivirus with broad cellular tropism expressing the same antigen in mice. The findings demonstrated that our novel recombinant DC-targeted lentivector was able to successfully transduce and express the fusion antigen Ag85A-E6 in vitro and in vivo. Moreover, a single footpad injection of targeted lentivectors could elicit strong T-helper 1 (Th1) immunity against the above mentioned antigen, as indicated by the specific high-level production of IFN-γ and IL-2 using spleen lymphocytes and lymphoproliferative responses. Despite of these promising results, more attempts are required to elucidate the protective and therapeutic efficacy of this approach in future.
Applied Biotechnology Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran.
Mehdi
M
Shakouri
Department of Immunology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran. Electronic address: moazzeni@modares.ac.ir.
Seyed Mohammad
SM
Moazzeni
Chemical Injuries Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran. Electronic address: mghanei@hbi.ir.
Mostafa
M
Ghanei
Department of Virology, Pasteur Institute of Iran, Tehran, Iran. Electronic address: a_arashkia@pasteur.ac.ir.
Arash
A
Arashkia
Department of Virology, Pasteur Institute of Iran, Tehran, Iran.
Mohammad Hossein
MH
Etemadzadeh
Department of Virology, Pasteur Institute of Iran, Tehran, Iran. Electronic address: azadmanesh@pasteur.ac.ir.
Kayhan
K
Azadmanesh
D000217:Acyltransferases / Q000276:immunology*; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D000942:Antigens, Bacterial / Q000276:immunology*; D001426:Bacterial Proteins / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D058501:Enzyme-Linked Immunospot Assay; D005260:Female; D005822:Genetic Vectors; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology; D016086:Lentivirus; D051379:Mice; D008807:Mice, Inbred BALB C; D009169:Mycobacterium tuberculosis / Q000276:immunology; D014161:Transduction, Genetic; D014376:Tuberculosis / Q000276:immunology / Q000517:prevention & control; D032581:Tuberculosis Vaccines / Q000276:immunology*; D014760:Viral Fusion Proteins / Q000276:immunology*
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; C093276:ESAT-6 protein, Mycobacterium tuberculosis; D032581:Tuberculosis Vaccines; D014760:Viral Fusion Proteins; D000217:Acyltransferases; C112580:antigen 85A, Mycobacterium tuberculosis
Cellular immunity; DC-targeted lentivector; Dendritic cell; Tuberculosis