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

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

doi:10.3389/fimmu.2018.00643

Cited by 16 publications

(7 citation statements)

References 64 publications

(70 reference statements)

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“…One promising approach for T cell induction is M. bovis BCG as a bacterial live recombinant vaccine vehicle. Specific humoral and cellular immune responses against HIV-1 have been detected after immunization of mice with recombinant BCG (rBCG) expressing HIV-1 antigens 20, 21, 22, 23, 24. We previously developed several rBCG HIV-1 vaccine candidates with the aim of inducing protective cell-mediated responses.…”

Section: Introductionmentioning

confidence: 99%

MTBVAC-Based TB-HIV Vaccine Is Safe, Elicits HIV-T Cell Responses, and Protects against Mycobacterium tuberculosis in Mice

Broset

Saubí

Guitart

et al. 2019

Molecular Therapy - Methods & Clinical Development

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The tuberculosis (TB) vaccine MTBVAC is the only live-attenuated Mycobacterium tuberculosis ( Mtb )-based vaccine in clinical development, and it confers superior protection in different animal models compared to the current vaccine, BCG ( Mycobacterium bovis bacillus Calmette-Guérin). With the aim of using MTBVAC as a vector for a dual TB-HIV vaccine, we constructed the recombinant MTBVAC.HIVA 2auxo strain. First, we generated a lysine auxotroph of MTBVAC (MTBVACΔ lys ) by deleting the lysA gene. Then the auxotrophic MTBVACΔ lys was transformed with the E. coli -mycobacterial vector p2auxo.HIVA, harboring the lysA -complementing gene and the HIV-1 clade A immunogen HIVA. This TB-HIV vaccine conferred similar efficacy to the parental strain MTBVAC against Mtb challenge in mice. MTBVAC.HIVA 2auxo was safer than BCG and MTBVAC in severe combined immunodeficiency (SCID) mice, and it was shown to be maintained up to 42 bacterial generations in vitro and up to 100 days after inoculation in vivo . The MTBVAC.HIVA 2auxo vaccine, boosted with modified vaccinia virus Ankara (MVA).HIVA, induced HIV-1 and Mtb -specific interferon-γ-producing T cell responses and polyfunctional HIV-1-specific CD8+ T cells producing interferon-γ (IFN-γ), tumor necrosis factor alpha (TNF-α), and CD107a in BALB/c mice. Here we describe new tools to develop combined vaccines against TB and HIV with the potential of expansion for other infectious diseases.

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Section: Introductionmentioning

confidence: 99%

MTBVAC-Based TB-HIV Vaccine Is Safe, Elicits HIV-T Cell Responses, and Protects against Mycobacterium tuberculosis in Mice

Broset

Saubí

Guitart

et al. 2019

Molecular Therapy - Methods & Clinical Development

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“…Antigens expressed by recombinant BCG (rBCG) strains can elicit long-lasting humoral and cellular immunity, including CD4 + and CD8 + T cell responses, to the foreign antigens in animals or humans. Recombinant BCG technology has been studied in the context of vaccination against HIV ( 39 , 40 ), HCV ( 41 ), hMPV ( 42 ), RSV ( 43 ), rotavirus ( 44 ), Bordetella pertussis ( 45 ), Lyme disease ( 46 ), malaria ( 47 ), and measles ( 48 ). Furthermore, when administered in early life, BCG vaccination can act as an adjuvant enhancing antibody responses to recombinant hepatitis B surface antigen (rHBsAg) both in mice and in human infants ( 49 , 50 ).…”

Section: Novel Bcg-based Approachesmentioning

confidence: 99%

The BCG Vaccine for COVID-19: First Verdict and Future Directions

González-Pérez

Sánchez-Tarjuelo

Shor³

et al. 2021

Front. Immunol.

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Despite of the rapid development of the vaccines against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), it will take several months to have enough doses and the proper infrastructure to vaccinate a good proportion of the world population. In this interim, the accessibility to the Bacille Calmette-Guerin (BCG) may mitigate the pandemic impact in some countries and the BCG vaccine offers significant advantages and flexibility in the way clinical vaccines are administered. BCG vaccination is a highly cost-effective intervention against tuberculosis (TB) and many low-and lower-middle-income countries would likely have the infrastructure, and health care personnel sufficiently familiar with the conventional TB vaccine to mount full-scale efforts to administer novel BCG-based vaccine for COVID-19. This suggests the potential for BCG to overcome future barriers to vaccine roll-out in the countries where health systems are fragile and where the effects of this new coronavirus could be catastrophic. Many studies have reported cross-protective effects of the BCG vaccine toward non-tuberculosis related diseases. Mechanistically, this cross-protective effect of the BCG vaccine can be explained, in part, by trained immunity, a recently discovered program of innate immune memory, which is characterized by non-permanent epigenetic reprogramming of macrophages that leads to increased inflammatory cytokine production and consequently potent immune responses. In this review, we summarize recent work highlighting the potential use of BCG for the treatment respiratory infectious diseases and ongoing SARS-CoV-2 clinical trials. In situations where no other specific prophylactic tools are available, the BCG vaccine could be used as a potential adjuvant, to decrease sickness of SARS-CoV-2 infection and/or to mitigate the effects of concurrent respiratory infections.

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“…23 Therefore, in this study, to elicit an anti-MIF immune response as an anticancer vaccine, we developed a recombinant Smeg vaccine delivering a fusion protein of human MIF and IL-7 (rSmeg-hMIF-hIL-7), which can act as a target antigen and an adjuvant of cancer vaccine, respectively, via a novel Mycobacterium-Escherichia coli shuttle vector system, pMyong2, to guarantee stable and enhanced expression of delivered heterologous genes in recombinant Smeg or BCG. 24 25 We also sought to explore the immunotherapeutic potential of rSmeg-hMIF-hIL-7 in a tumor-bearing mouse model system. We found that rSmeg-hMIF-hIL-7 treatment led to a significant cancer inhibitory effect mainly by restoring the CTL response in tumor microenvironments by inducing anti-MIF immune responses.…”

Section: Introductionmentioning

confidence: 99%

Recombinant Mycobacterium smegmatis delivering a fusion protein of human macrophage migration inhibitory factor (MIF) and IL-7 exerts an anticancer effect by inducing an immune response against MIF in a tumor-bearing mouse model

Jeong

Lee

Seo

et al. 2021

J Immunother Cancer

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BackgroundMacrophage migration inhibitory factor (MIF) is a pleotropic inflammatory cytokine that is overexpressed in a number of cancer types including most types of human cancer. Inhibition of MIF signaling can restore anticancer immune responses in tumor microenvironments. In this study, we aimed to develop a therapeutic vaccine capable of inhibiting tumor development by inducing anti-MIF immune responses.MethodsWe introduced a recombinant Mycobacterium smegmatis (rSmeg-hMIF-hIL-7) vaccine that could deliver a fusion protein of human macrophage migration inhibitory factor (MIF) and interleukin 7, which could act as a target antigen and as an adjuvant of cancer vaccine, respectively. We checked the anticancer potential of the vaccine in a tumor-bearing mouse model.ResultsWe found that rSmeg-hMIF-hIL-7 showed enhanced oncolytic activity compared with PBS, BCG or Smeg in MC38-bearing mice, and there was an increase in the humoral and cell-mediated immune responses against MIF. rSmeg-hMIF-hIL-7 can also induce a neutralizing effect regarding MIF tautomerase activity in the serum of vaccinated mice. We also found downregulation of MIF, CD74, and CD44, which are related to the MIF signaling pathway and PI3K/Akt and MMP2/9 signaling, which are regulated by MIF in the tumor tissue of rSmeg-hMIF-hIL-7-vaccinated mice, suggesting a significant role of the anti-MIF immune response to rSmeg-hMIF-hIL-7 in its anticancer effect. In addition, rSmeg-hMIF-hIL-7 treatment led to enhanced activation of CD4+ and CD8+ T cells in the tumor regions of vaccinated mice, also contributing to the anticancer effect. This trend was also found in LLC-bearing and PanO2-bearing mouse models. In addition, rSmeg-hMIF-hIL-7 treatment exerted an enhanced anticancer effect with one of the immune checkpoint inhibitors, the anti-PD-L1 antibody, in a tumor-bearing mouse model.ConclusionsIn conclusion, our data showed that rSmeg-hMIF-hIL-7 exerts a strong antitumor immune response in mice, possibly by inhibiting the MIF-dependent promotion of tumorigenesis by the anti-MIF immune response and via enhanced cytotoxic T cell recruitment into tumor microenvironments. We also found that it also exerted an enhanced anticancer effect with immune checkpoint inhibitors. These results suggest that rSmeg-hMIF-hIL-7 is a potential adjuvant for cancer immunotherapy. This is the first report to prove anticancer potential of immunotherapeutic vaccine targeting immune response against MIF.

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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

Cited by 16 publications

References 64 publications

MTBVAC-Based TB-HIV Vaccine Is Safe, Elicits HIV-T Cell Responses, and Protects against Mycobacterium tuberculosis in Mice

MTBVAC-Based TB-HIV Vaccine Is Safe, Elicits HIV-T Cell Responses, and Protects against Mycobacterium tuberculosis in Mice

The BCG Vaccine for COVID-19: First Verdict and Future Directions

Recombinant Mycobacterium smegmatis delivering a fusion protein of human macrophage migration inhibitory factor (MIF) and IL-7 exerts an anticancer effect by inducing an immune response against MIF in a tumor-bearing mouse model

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