Abstract
Recombinant Mycobacterium strains such as recombinant BCG (rBCG) have received considerable attention for the HIV-1 vaccine development. Recently, we described a temperature-sensitive Mycobacterium paragordonae (Mpg) strain as a novel live tuberculosis vaccine that is safer and showed an enhanced protective effect against mycobacterial infection compared to BCG. We studied the possibility of developing a vaccine against HIV-1 infection using rMpg strain expressing the p24 antigen (rMpg-p24). We observed that rMpg-p24 can induce an increased p24 expression in infected antigen presenting cells (APCs) compared to rBCG-p24. We also observed that rMpg-p24 can induce enhanced p24 specific immune responses in vaccinated mice as evidenced by increased p24-specific T lymphocyte proliferation, gamma interferon induction, antibody production and cytotoxic T lymphocyte (CTL) responses. Furthermore, an rMpg-p24 prime and plasmid DNA boost showed an increased CTL response and antibody production compared to rBCG or rMpg alone. In summary, our study indicates that a live rMpg-p24 strain induced enhanced immune responses against HIV-1 Gag in vaccinated mice. Thus, rMpg-p24 may have potential as a preventive prime vaccine in a heterologous prime-boost regimen for HIV-1 infection.
Highlights
The effective control of HIV replication in infected patients is currently achieved via highly active antiretroviral therapy (HAART)
Our results indicate that the developed rMpg-p24 strain showed stable p24 expression within the recombinant bacteria and led to an enhanced production of p24 protein in infected bone-marrow derived dendritic cells (BMDCs) compared to that observed in cells infected with Recombinant bacille Calmette-Guérin (BCG) (rBCG)-p24
Our data showed that the amount of p24 expressed by bacteria was almost similar between the two recombinant bacteria, the amount of p24 delivered into BMDCs by rMpg-p24 was higher than that observed for rBCG-p24 (Fig. 2c), which could enhance the levels of p24-derived peptides presented to T cells
Summary
The effective control of HIV replication in infected patients is currently achieved via highly active antiretroviral therapy (HAART). Our further studies described that compared to BCG, Mpg was safer in infected cells and mice and exerted an enhanced protective effect against M. tuberculosis or even M. abscessus infection[18] demonstrating the potential of rMpg for vaccine development as an alternative to rBCG. To explore this possibility, in the present study, we first developed an rMpg-p24 strain expressing HIV-1 Gag p24 proteins and compared its capacity to induce p24-specific immune responses with rBCG-p24 in mice vaccinated with mycobacteria alone. We explored whether the p24-specific immune response elicited by rMpg-P24 could be augmented by boosting with a p24- encoding plasmid DNA vaccine
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