Thirty years of recombinant BCG: new trends for a centenary vaccine

2021 ◽  
Author(s):  
Lazaro M Marques-Neto ◽  
Zuzanna Piwowarska ◽  
Alex I. Kanno ◽  
Luana Moraes ◽  
Monalisa M Trentini ◽  
...  
Keyword(s):  
Recombinant Bcg

Author response for "MHC‐restricted Ag85B‐specific CD8 + T cells are enhanced by recombinant BCG prime and DNA boost immunization in mice"

2019 ◽  
Author(s):  
Shihoko Komine‐Aizawa ◽  
Jiansheng Jiang ◽  
Satoru Mizuno ◽  
Satoshi Hayakawa ◽  
Kazuhiro Matsuo ◽  
...  
Keyword(s):  
T Cells ◽  
Author Response ◽  
Boost Immunization ◽  
Recombinant Bcg

scholarly journals A recombinant selective drug-resistant M. bovis BCG enhances the bactericidal activity of a second-line tuberculosis regimen

2021 ◽  
Author(s):  
Gift Chiwala ◽  
Zhiyong Liu ◽  
Julius N. Mugweru ◽  
Bangxing Wang ◽  
Shahzad Akbar Khan ◽  
...  
Keyword(s):  
Chemotherapy Regimen ◽  
Therapeutic Vaccine ◽  
Drug Resistant ◽  
Second Line ◽  
Therapeutic Vaccines ◽  
Resistant Tuberculosis ◽  
Colony Forming Units ◽  
Pathogen Clearance ◽  
Deficient Mice ◽  
Recombinant Bcg

AbstractDrug-resistant tuberculosis (DR-TB) results from infection by Mycobacterium tuberculosis strains resistant to at least rifampin or isoniazid. To improve the treatment outcome in DR-TB, therapeutic vaccines are considered an ideal choice as they can enhance pathogen clearance and minimize disease sequelae. To date, there is no therapeutic vaccine reported to be effective when combined with a chemotherapy regimen against DR-TB. The only available TB vaccine, the M. bovis BCG (BCG) is susceptible to several anti-TB drugs hence not a perfect option for therapeutic vaccination. Herein, we developed a recombinant BCG (RdrBCG) overexpressing Ag85B and Rv2628 with resistance to selected anti-TB drugs. When administered three times adjunct to a second-line anti-TB regimen in a classical murine model of DR-TB, the RdrBCG lowered lung M. tuberculosis colony-forming units by 1 log10. Furthermore, vaccination with the RdrBCG adjunct to TB chemotherapy minimized lung tissue pathology in mice. Most importantly, the RdrBCG maintained the exogenously inserted genes and showed almost the same virulence as its parent BCG Tice strain in severe combined immune-deficient mice. All these suggested that the RdrBCG was stable, safe and effective. Hence, the “recombinant” plus “drug-resistant” BCG strategy could be a useful concept for developing therapeutic vaccines against DR-TB.

scholarly journals The role of TLR-4 in the immunomodulatory effects of recombinant BCG expressing MSP-1C of Plasmodium falciparum

2019 ◽  
Vol 13 (11) ◽  
pp. 1057-1061
Author(s):  
Muhammad Adamu Abbas ◽  
Rapeah Suppian
Keyword(s):  
Nitric Oxide ◽  
Plasmodium Falciparum ◽  
Inflammatory Responses ◽  
Peritoneal Macrophages ◽  
Significant Inhibition ◽  
Immunomodulatory Effects ◽  
Attachment Mechanism ◽  
Significant Production ◽  
Recombinant Bcg

Introduction: An earlier constructed recombinant BCG expressing the MSP-1C of Plasmodium falciparum, induced inflammatory responses leading to significant production of nitric oxide (NO) alongside higher expression of the enzyme inducible nitric oxide synthase (iNOS) and significant production of the regulatory cytokine, IL-10, indicating significant immunomodulatory effects of the construct. The mechanism of these responses had not been established but is thought to involve toll-like receptor 4 (TLR-4). Methodology: The present study was carried out to determine the role of TLR-4 on eliciting the immunomodulatory effects of recombinant BCG expressing MSP-1C of Plasmodium falciparum leading to the production of NO and IL-10, as well as the expression of iNOS. Six groups of mice (n = 6 per group) were immunised thrice, three weeks apart with intraperitoneal phosphate buffered saline T80 (PBS-T80), BCG or rBCG in the presence or absence of a TLR-4 inhibitor; TAK-242, given one hour prior to each immunisation. Peritoneal macrophages were harvested from the mice and cultured for the determination of NO, iNOS and IL-10 via Griess assay, ELISA and Western blot respectively. Results: The results showed significant inhibition of the production of NO and IL-10 and the expression of iNOS in all groups of mice in the presence of TAK-242. Conclusions: These results presented evidence of the role of TLR-4/rBCG attachment mechanism in modulating the production of NO and IL-10 and the expression of iNOS in response to our rBCG-based malaria vaccine candidate expressing MSP-1C of P. falciparum.

Recombinant BCG-Rv1767 amount determines, in vivo, antigen-specific T cells location, frequency, and protective outcome

2010 ◽  
Vol 48 (5) ◽  
pp. 150-159 ◽  
Author(s):  
Viviana Speranza ◽  
Alessia Colone ◽  
Rosella Cicconi ◽  
Graziana Palmieri ◽  
Daniela Giovannini ◽  
...  
Keyword(s):  
T Cells ◽  
Recombinant Bcg

scholarly journals Recombinant BCG Expressing HTI Prime and Recombinant ChAdOx1 Boost Is Safe and Elicits HIV-1-Specific T-Cell Responses in BALB/c Mice

Vaccines ◽  
2019 ◽  
Vol 7 (3) ◽  
pp. 78 ◽  
Author(s):  
Athina Kilpeläinen ◽  
Narcís Saubi ◽  
Núria Guitart ◽  
Alex Olvera ◽  
Tomáš Hanke ◽  
...  
Keyword(s):  
T Cell ◽  
Miliary Tuberculosis ◽  
T Cell Responses ◽  
T Cell Response ◽  
Expression Vectors ◽  
Effective Vaccine ◽  
Vaccine Platform ◽  
Cell Responses ◽  
Hiv 1 ◽  
Recombinant Bcg

Despite the availability of anti-retroviral therapy, HIV-1 infection remains a massive burden on healthcare systems. Bacillus Calmette-Guérin (BCG), the only licensed vaccine against tuberculosis, confers protection against meningitis and miliary tuberculosis in infants. Recombinant BCG has been used as a vaccine vehicle to express both HIV-1 and Simian Immunodeficiemcy Virus (SIV) immunogens. In this study, we constructed an integrative E. coli-mycobacterial shuttle plasmid, p2auxo.HTI.int, expressing the HIVACAT T-cell immunogen (HTI). The plasmid was transformed into a lysine auxotrophic Mycobacterium bovis BCG strain (BCGΔLys) to generate the vaccine BCG.HTI2auxo.int. The DNA sequence coding for the HTI immunogen and HTI protein expression were confirmed, and working vaccine stocks were genetically and phenotypically characterized. We demonstrated that the vaccine was stable in vitro for 35 bacterial generations, and that when delivered in combination with chimpanzee adenovirus (ChAd)Ox1.HTI in adult BALB/c mice, it was well tolerated and induced HIV-1-specific T-cell responses. Specifically, priming with BCG.HTI2auxo.int doubled the magnitude of the T-cell response in comparison with ChAdOx1.HTI alone while maintaining its breadth. The use of integrative expression vectors and novel HIV-1 immunogens can aid in improving mycobacterial vaccine stability as well as specific immunogenicity. This vaccine candidate may be a useful tool in the development of an effective vaccine platform for priming protective responses against HIV-1/TB and other prevalent pediatric pathogens.

scholarly journals Stable Expression of Lentiviral Antigens by Quality-Controlled Recombinant Mycobacterium bovis BCG Vectors

2015 ◽  
Vol 22 (7) ◽  
pp. 726-741 ◽  
Author(s):  
Bryan E. Hart ◽  
Rose Asrican ◽  
So-Yon Lim ◽  
Jaimie D. Sixsmith ◽  
Regy Lukose ◽  
...  
Keyword(s):  
Mycobacterium Bovis ◽  
Antigen Expression ◽  
Full Length ◽  
Content Type ◽  
Immunodeficiency Virus ◽  
Vaccine Stability ◽  
Hiv Gp120 ◽  
Recombinant Bcg

ABSTRACTThe well-established safety profile of the tuberculosis vaccine strain,Mycobacterium bovisbacille Calmette-Guérin (BCG), makes it an attractive vehicle for heterologous expression of antigens from clinically relevant pathogens. However, successful generation of recombinant BCG strains possessing consistent insert expression has encountered challenges in stability. Here, we describe a method for the development of large recombinant BCG accession lots which stably express the lentiviral antigens, human immunodeficiency virus (HIV) gp120 and simian immunodeficiency virus (SIV) Gag, using selectable leucine auxotrophic complementation. Successful establishment of vaccine stability stems from stringent quality control criteria which not only screen for highly stable complemented BCG ΔleuCDtransformants but also thoroughly characterize postproduction quality. These parameters include consistent production of correctly sized antigen, retention of sequence-pure plasmid DNA, freeze-thaw recovery, enumeration of CFU, and assessment of cellular aggregates. Importantly, these quality assurance procedures were indicative of overall vaccine stability, were predictive for successful antigen expression in subsequent passaging bothin vitroandin vivo, and correlated with induction of immune responses in murine models. This study has yielded a quality-controlled BCG ΔleuCDvaccine expressing HIV gp120 that retained stable full-length expression after 1024-fold amplificationin vitroand following 60 days of growth in mice. A second vaccine lot expressed full-length SIV Gag for >1068-fold amplificationin vitroand induced potent antigen-specific T cell populations in vaccinated mice. Production of large, well-defined recombinant BCG ΔleuCDlots can allow confidence that vaccine materials for immunogenicity and protection studies are not negatively affected by instability or differences between freshly grown production batches.

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