Abstract
Even though the rate of new human immunodeficiency virus type 1 (HIV-1) infections is gradually decreasing worldwide, an effective preventive vaccine for HIV-1 is still urgently needed. The recombinant Mycobacterium bovis BCG (rBCG) is promising for the development of an HIV-1 vaccine. Recently, we showed that a recombinant Mycobacterium smegmatis expressing HIV-1 gag in a pMyong2 vector system (rSmeg-pMyong2-p24) increased the efficacy of a vaccine against HIV-1 in mice. Here, we evaluated the potential of an rBCG expressing HIV-1 p24 antigen Gag in pMyong2 (rBCG-pMyong2-p24) in a vaccine application for HIV-1 infection. We found that rBCG-pMyong2-p24 elicited an enhanced HIV-1 p24 Gag expression in rBCG and infected antigen-presenting cells. We also found that compared to rBCG-pAL-p24 in a pAL5000 derived vector system, rBCG-pMyong2-p24 elicited enhanced p24-specific immune responses in vaccinated mice as evidenced by higher levels of HIV-1 Gag-specific CD4 and CD8 T lymphocyte proliferation, gamma interferon ELISPOT cell induction, antibody production, and cytotoxic T lymphocytes (CTL) responses. Furthermore, rBCG-pMyong2-p24 showed a higher level of p24-specific Ab production than rSmeg-pMyong2-p24 in the same pMyong2 vector system. In conclusion, our data indicated that a live recombinant BCG expressing HIV-1 Gag using a pMyong2 vector system, rBCG-pMyong2-p24 elicited an enhanced immune response against HIV-1 infections in a mouse model system. So, rBCG-pMyong2-p24 may have the potential as a prime vaccine in a heterologous prime-boost vaccine strategy for HIV-1 infection.
Highlights
Despite the contribution of highly activated antiretroviral therapy in controlling human immunodeficiency virus (HIV) replication in infected individuals [1, 2], 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 [33,34,35,36,37], 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 (rBCG) compared to that using the conventional pAL5000 vector system which was originated from M. fortuitum [38, 39]
To compare the p24 expression levels according to the different M.O.I., bone marrow-derived dendritic cells (BMDCs) were infected with different M.O.I. (1 and 10 M.O.I.) of rBCG-pAL-p24 and rBCG-pMyong2-p24 for 1 and 3 days
Summary
Despite the contribution of highly activated antiretroviral therapy in controlling human immunodeficiency virus (HIV) replication in infected individuals [1, 2], several problems, including the emergence of drug-resistant viruses after long-term treatment and expensive drug costs, remain to be resolved. Since an effective immune response against HIV-1 can arise, characterized by HIVspecific T cells with poly-functionality and capacity to proliferate against both the immunodominant viral peptides [5,6,7], cellular immunity, virus-specific cytotoxic T lymphocytes (CTL), should be a more important component of the host immune system for protection against HIV-1. Based on these findings, several strategies, including the use of live viral vectors and plasmid DNA vaccines, are in development to elicit strong HIV-1-specific CTL and Th1 type response. Since BCG can prevent disseminated disease in children, it has been used as a part of the World Health Organization Expanded Program on Immunization for childhood vaccination since the early 1970s [15, 16]
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