BCG vaccination induces cross-protective immunity against pathogenic microorganisms

Soto, Jorge A.; Gálvez, Nicolás M. S.; Andrade, Catalina A; Ramírez, Mario A.; Riedel, Claudia A.; Kalergis, Alexis M.; Bueno, Susan M.

doi:10.1016/j.it.2021.12.006

Cited by 35 publications

(33 citation statements)

References 89 publications

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“…Mycobacterium bovis Bacillus Calmette-Guérin (BCG) is an attenuated strain of M. bovis , obtained after about 230 in vitro passages, and the only current vaccine for the prevention and treatment of the infection caused by M. tb [ 1 , 2 , 3 ]. This live-attenuated vaccine has been widely used for over a century to prevent tuberculosis disease, and it is one of the most used vaccines worldwide, with a well-characterized and documented safety profile [ 4 , 5 ].…”

Section: Discussionmentioning

confidence: 99%

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BCG-Based Vaccines Elicit Antigen-Specific Adaptive and Trained Immunity against SARS-CoV-2 and Andes orthohantavirus

et al. 2022

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Background:Mycobacterium bovis Bacillus Calmette-Guérin (BCG) is a live attenuated vaccine mainly administered to newborns and used for over 100 years to prevent the disease caused by Mycobacterium tuberculosis (M. tb). This vaccine can induce immune response polarization towards a Th1 profile, which is desired for counteracting M. tb, other mycobacteria, and unrelated intracellular pathogens. The vaccine BCG has been used as a vector to express recombinant proteins and has been shown to protect against several diseases, particularly respiratory viruses. Methods: BCG was used to develop recombinant vaccines expressing either the Nucleoprotein from SARS-CoV-2 or Andes orthohantavirus. Mice were immunized with these vaccines with the aim of evaluating the safety and immunogenicity parameters. Results: Immunization with two doses of 1 × 108 CFU or one dose of 1 × 105 CFU of these BCGs was safe in mice. A statistically significant cellular immune response was induced by both formulations, characterized as the activation of CD4+ and CD8+ T cells. Stimulation with unrelated antigens resulted in increased expression of activation markers by T cells and secretion of IL-2 and IFN-γ, while increased secretion of IL-6 was found for both recombinant vaccines; all of these parameters related to a trained immunity profile. The humoral immune response elicited by both vaccines was modest, but further exposure to antigens could increase this response. Conclusions: The BCG vaccine is a promising platform for developing vaccines against different pathogens, inducing a marked antigen-specific immune response.

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Section: Discussionmentioning

confidence: 99%

“…Mycobacterium bovis Bacillus Calmette-Guérin (BCG) is an attenuated strain of M. bovis and the only available vaccine for preventing and treating the infection caused by M. tuberculosis [ 1 , 2 , 3 ]. This live-attenuated vaccine has been widely used since 1921, and it is one of the most used vaccines worldwide [ 4 , 5 ].…”

Section: Introductionmentioning

confidence: 99%

BCG-Based Vaccines Elicit Antigen-Specific Adaptive and Trained Immunity against SARS-CoV-2 and Andes orthohantavirus

et al. 2022

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“…The increase in IFN-γ concentration can be interpreted as a positive result because this cytokine can be beneficial against hRSV [22]- [24]. This response is short-lived, may be dosedependent [12], [13], [25] and is consistent with the notion that BCG can induce T H 1 responses in humans [26]- [28], which is one of the reasons as to why it was selected as a vector for immunizing against hRSV antigens [7]- [11], [13], [29], [30].…”

Section: Discussionmentioning

confidence: 99%

“…One of the current vaccine candidates against hRSV is rBCG-N-hRSV, a vaccine based on an attenuated Mycobacterium bovis Bacillus Calmette-Guérin (BCG) that recombinantly expresses the nucleoprotein of hRSV (N-hRSV) [7]– [11]. The design of this vaccine is highly advantageous as BCG is one of the oldest and safest vaccines used to date and is currently applied to newborns to prevent tuberculosis in most countries [12], [13]. Thus, this BCG strain could potentially grant protection against both tuberculosis and hRSV in newborns, which represent the most at-risk population of hRSV-caused ALRTIs.…”

Section: Introductionmentioning

confidence: 99%

A recombinant BCG-based vaccine against the human respiratory syncytial virus induces a balanced cellular immune response against viral and mycobacterial antigens

Pacheco

Gálvez

Andrade

et al. 2022

Preprint

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BACKGROUND: The human respiratory syncytial virus (hRSV) is a respiratory pathogen responsible for most cases of acute lower respiratory tract infections in infants worldwide. Although this virus represents a significant social and economic burden, there are no safe and effective available vaccines. rBCG-N-hRSV is a vaccine candidate consisting of a recombinant attenuated Mycobacterium bovis Bacillus Calmette-Guerin (BCG) expressing the nucleoprotein of hRSV (N-hRSV). METHODS: rBCG-N-hRSV was applied intradermally in three different doses (5x103, 5x104, or 1x105 CFU) to healthy adults enrolled in a randomized, double-blind, dose-escalating phase 1 clinical trial (NCT03213405). Blood samples were taken before and at various time points after immunization. Cellular and humoral immune parameters were assessed by analyzing circulating immune cells and sera, respectively. RESULTS: Perforin- and Granzyme B-producing PBMCs recognizing viral or mycobacterial antigens were found to increase after immunization with rBCG-N-hRSV. These cells also upregulated IFN-g; and IL-10 secretion in response to N-hRSV and upregulated IFNg, IL-6, and TNF-a; secretion in response to mycobacterial proteins. While naive T cell populations contracted over time, no specific memory T cell subset expanded significantly. Although binding to C1q by anti-N-hRSV or anti-mycobacterial antibodies decreased slightly after immunization, no apparent changes were found in the concentration of IgG subclasses against N-hRSV or mycobacterial antigens. CONCLUSIONS: The immune response elicited by immunization with rBCG-N-hRSV consists mainly of antigen-specific T cells. The data reported here provide novel information about the characteristics of the immune response elicited after immunization with rBCG-N-hRSV, supporting the safety and immunogenicity of this vaccine.

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“…The Mycobacterium bovis ( M. Bovis ) strain, referred to as Bacillus Calmette-Guerin (BCG), is an attenuated version of a known species belonging to the M. tuberculosis complex [ 14 ]. Although infections with BCG do not recapitulate all pathological features observed with M. tuberculosis , BCG is a valuable model for studying anti-mycobacterial immune responses mimicking important aspects of bacilli-host interaction [ 15 , 16 ].…”

Section: Introductionmentioning

confidence: 99%

Increased Heme Oxygenase 1 Expression upon a Primary Exposure to the Respiratory Syncytial Virus and a Secondary Mycobacterium bovis Infection

et al. 2022

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The human respiratory syncytial virus (hRSV) is the leading cause of severe lower respiratory tract infections in infants. Because recurrent epidemics based on reinfection occur in children and adults, hRSV has gained interest as a potential primary pathogen favoring secondary opportunistic infections. Several infection models have shown different mechanisms by which hRSV promotes immunopathology to prevent the development of adaptive protective immunity. However, little is known about the long-lasting effects of viral infection on pulmonary immune surveillance mechanisms. As a first approach, here we evaluated whether a primary infection by hRSV, once resolved, dampens the host immune response to a secondary infection with an attenuated strain of Mycobacterium bovis (M. Bovis) strain referred as to Bacillus Calmette-Guerin (BCG). We analyzed leukocyte dynamics and immunomodulatory molecules in the lungs after eleven- and twenty-one-days post-infection with Mycobacterium, using previous hRSV infected mice, by flow cytometry and the expression of critical genes involved in the immune response by real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR). Among the latter, we analyzed the expression of Heme Oxygenase (HO)-1 in an immunization scheme in mice. Our data suggest that a pre-infection with hRSV has a conditioning effect promoting lung pathology during a subsequent mycobacterial challenge, characterized by increased infiltration of innate immune cells, including interstitial and alveolar macrophages. Our data also suggest that hRSV impairs pulmonary immune responses, promoting secondary mycobacterial colonization and lung survival, which could be associated with an increase in the expression of HO-1. Additionally, BCG is a commonly used vaccine that can be used as a platform for the generation of new recombinant vaccines, such as a recombinant BCG strain expressing the nucleoprotein of hRSV (rBCG-N-hRSV). Therefore, we evaluated if the immunization with rBCG-N-hRSV could modulate the expression of HO-1. We found a differential expression pattern for HO-1, where a higher induction of HO-1 was detected on epithelial cells compared to dendritic cells during late infection times. This is the first study to demonstrate that infection with hRSV produces damage in the lung epithelium, promoting subsequent mycobacterial colonization, characterized by an increase in the neutrophils and alveolar macrophages recruitment. Moreover, we determined that immunization with rBCG-N-hRSV modulates differentially the expression of HO-1 on immune and epithelial cells, which could be involved in the repair of pulmonary tissue.

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BCG vaccination induces cross-protective immunity against pathogenic microorganisms

Cited by 35 publications

References 89 publications

BCG-Based Vaccines Elicit Antigen-Specific Adaptive and Trained Immunity against SARS-CoV-2 and Andes orthohantavirus

BCG-Based Vaccines Elicit Antigen-Specific Adaptive and Trained Immunity against SARS-CoV-2 and Andes orthohantavirus

A recombinant BCG-based vaccine against the human respiratory syncytial virus induces a balanced cellular immune response against viral and mycobacterial antigens

Increased Heme Oxygenase 1 Expression upon a Primary Exposure to the Respiratory Syncytial Virus and a Secondary Mycobacterium bovis Infection

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