Development of a Live Recombinant BCG Expressing Human Immunodeficiency Virus Type 1 (HIV-1) Gag Using a pMyong2 Vector System: Potential Use As a Novel HIV-1 Vaccine

We showed that a recombinant Mycobacterium smegmatis expressing human immunodeficiency virus type 1 gag in a pMyong2 vector system increased the efficacy of a vaccine against HIV-1 in mice

Byoung-Jun Kim; Bo-Ram Kim; Yoon-Hoh Kook; Bum-Joon Kim

2018

Scholarcy highlights

  • Despite the contribution of highly activated antiretroviral therapy in controlling human immunodeficiency virus replication in infected individuals, several problems, including the emergence of drug-resistant viruses after long-term treatment and expensive drug costs, remain to be resolved
  • By conducting a genome analysis of M. yongonense DSM 45126T, we introduced a novel Mycobacterium–Escherichia coli shuttle vector system using the mycobacterial replicon of pMyong2, which is a linear plasmid within its genome that can lead to increased heterologous gene expression in recombinant M. smegmatis and recombinant Mycobacterium bovis BCG compared to that using the conventional pAL5000 vector system which was originated from M. fortuitum
  • The best strategy reported to improve the potential of rBCG as an HIV vaccine is its use as a prime vaccine in a prime-booster vaccine protocol using a safe recombinant viral vector for a booster vaccine, which has been shown to induce a long-lasting effective virus-specific cellular immunity after vaccination in animal models
  • Several strategies, including the use of a hemolysin-expressing BCG strain capable of eliciting a greater cytotoxic T lymphocytes response via the preferential cytosol location of rBCG and a codon optimization for the human immunodeficiency virus type 1 gag p24 gene in the rBCG system have been introduced
  • We applied the pMyong2 shuttle vector system to enhance the expression of the HIV-1 gag p24 gene in the rBCG, which has already been shown to be useful in recombinant M. smegmatis in our previous study
  • We found that rBCG-pMyong2-p24 produced more P24 proteins in the infected macrophages and bone marrow-derived dendritic cells than the conventional episomal pAL5000 vector and integrating pMV306 vector, providing a mechanistic basis of the enhanced virus-specific vaccine efficacy of rBCG-pMyong2-p24, including enhanced p24-specific T cell proliferation of BMDCs, T cell effector function, in CTLs, and Th1-biased humoral immune response
  • We showed that this strain could enhance the T cell proliferation capacity of infected bone marrow-derived dendritic cells and elicit improved cytotoxic T lymphocytes responses and Th1-biased humoral immune responses in vaccinated mice, compared to recombinant Mycobacterium bovis BCG-pAL-p24

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