Induction of Functional Specific Antibodies, IgG-Secreting Plasmablasts and Memory B Cells Following BCG Vaccination

Bitencourt, Júlia Valéria de Oliveira Vargas; Peralta-Álvarez, Marco Polo; Wilkie, Morven; Jacobs, Adam; Wright, Daniel; Almujri, Salem Salman; Li, Shuailin; Harris, Stephanie A.; Smith, Steven G.; Elias, Sean C.; White, Andrew Dickson; Satti, Iman; Sharpe, Sally; O’Shea, Matthew K.; McShane, Helen; Tanner, Rachel

doi:10.3389/fimmu.2021.798207

Cited by 12 publications

(15 citation statements)

References 85 publications

(107 reference statements)

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“…The cellular immune response is critical in host resistance to M. tuberculosis . However, more and more evidence indicates that the humoral immune response also plays an essential role in killing M. tuberculosis ( Bitencourt et al., 2021 ; Gong et al., 2022 ; Nziza et al., 2022 ). This study explored the humoral immunity induced by the MP3RT vaccine.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of the consistence between the results of immunoinformatics predictions and real-world animal experiments of a new tuberculosis vaccine MP3RT

Cheng

Xue²,

Wang³

et al. 2022

Front. Cell. Infect. Microbiol.

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BackgroundOur previous study developed a novel peptide-based vaccine, MP3RT, to fight against tuberculosis (TB) infection in a mouse model. However, the consistency between the immunoinformatics predictions and the results of real-world animal experiments on the MP3RT vaccine remains unclear.MethodIn this study, we predicted the antigenicity, immunogenicity, physicochemical parameters, secondary structure, and tertiary structure of MP3RT using bioinformatics technologies. The immune response properties of the MP3RT vaccine were then predicted using the C-ImmSim server. Finally, humanized mice were used to verify the characteristics of the humoral and cellular immune responses induced by the MP3RT vaccine.ResultsMP3RT is a non-toxic and non-allergenic vaccine with an antigenicity index of 0.88 and an immunogenicity index of 0.61, respectively. Our results showed that the MP3RT vaccine contained 53.36% α-helix in the secondary structure, and the favored region accounted for 98.22% in the optimized tertiary structure. The binding affinities of the MP3RT vaccine to the human leukocyte antigen (HLA)-DRB1*01:01 allele, toll-like receptor-2 (TLR-2), and TLR-4 receptors were -1234.1 kcal/mol, -1066.4 kcal/mol, and -1250.4 kcal/mol, respectively. The results of the C-ImmSim server showed that the MP3RT vaccine could stimulate T and B cells to produce immune responses, such as high levels of IgM and IgG antibodies, IFN-γ, TNF-α, and IL-2 cytokines. Results from real-world animal experiments showed that the MP3RT vaccine could stimulate the humanized mice to produce high levels of IgG and IgG2a antibodies and IFN-γ+ T lymphocytes. Furthermore, the levels of IFN-γ, IL-2, and IL-6 cytokines in mice immunized with the MP3RT vaccine were significantly higher than those in the control group.ConclusionMP3RT is a highly antigenic and immunogenic potential vaccine that can effectively induce Th1-type immune responses in silico analysis and animal experiments. This study lays the foundation for evaluating the value of computational tools and immunoinformatic techniques in reverse vaccinology research.

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Section: Discussionmentioning

confidence: 99%

Evaluation of the consistence between the results of immunoinformatics predictions and real-world animal experiments of a new tuberculosis vaccine MP3RT

Cheng

Xue²,

Wang³

et al. 2022

Front. Cell. Infect. Microbiol.

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“…In another NHP study, intravenous BCG drove superior antibody responses in the plasma and lungs of rhesus macaques compared to the traditional intradermal route and the IgM titers negatively correlated with Mtb burden (58). In a combined human and NHP study, BCG-driven induction of specific antibodies was shown to be comparable across humans and macaques, both in magnitude and the range of mycobacterial fractions (59). The study also showed the rapid and transient induction of antibody-secreting plasmablasts following BCG vaccination and via the use of in vitro functional assays identified a potential FcgR-mediated contribution of antibodies to the control of mycobacterial growth.…”

Section: B Cells and Antibody Responses To Bcg Vaccinationmentioning

confidence: 97%

A century of BCG vaccination: Immune mechanisms, animal models, non-traditional routes and implications for COVID-19

et al. 2022

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Bacillus Calmette-Guerin (BCG) has been used as a vaccine against tuberculosis since 1921 and remains the only currently approved vaccine for this infection. The recent discovery that BCG protects against initial infection, and not just against progression from latent to active disease, has significant implications for ongoing research into the immune mechanisms that are relevant to generate a solid host defense against Mycobacterium tuberculosis (Mtb). In this review, we first explore the different components of immunity that are augmented after BCG vaccination. Next, we summarize current efforts to improve the efficacy of BCG through the development of recombinant strains, heterologous prime-boost approaches and the deployment of non-traditional routes. These efforts have included the development of new recombinant BCG strains, and various strategies for expression of important antigens such as those deleted during the M. bovis attenuation process or antigens that are present only in Mtb. BCG is typically administered via the intradermal route, raising questions about whether this could account for its apparent failure to generate long-lasting immunological memory in the lungs and the inconsistent level of protection against pulmonary tuberculosis in adults. Recent years have seen a resurgence of interest in the mucosal and intravenous delivery routes as they have been shown to induce a better immune response both in the systemic and mucosal compartments. Finally, we discuss the potential benefits of the ability of BCG to confer trained immunity in a non-specific manner by broadly stimulating a host immunity resulting in a generalized survival benefit in neonates and the elderly, while potentially offering benefits for the control of new and emerging infectious diseases such as COVID-19. Given that BCG will likely continue to be widely used well into the future, it remains of critical importance to better understand the immune responses driven by it and how to leverage these for the design of improved vaccination strategies against tuberculosis.

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“…Moreover, antibodies are produced against a variety of M. tuberculosis antigens in human and animal models, and total and mycobacterial-specific antibody glycosylation patterns correlate with the effective control of M. tuberculosis infection and may distinguish patients with active TB disease from subjects with latent TB infection (LTBI) [ 11 , 17 ]. Finally, a recent study in rhesus macaques found that following intravenous BCG vaccination, IgM antibody levels in the plasma and bronchoalveolar lavage were the best indicators of protection against M. tuberculosis challenge [ 18 ].…”

Section: Introductionmentioning

confidence: 99%

Impact of Mycobacterium tuberculosis Infection on Human B Cell Compartment and Antibody Responses

Manna

Azgomi

Badami

et al. 2022

Cells

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Tuberculosis (TB) remains one of the most important health challenges worldwide. Control of the TB epidemic has not yet been achieved because of the lack of an effective vaccine and rapid and sensitive diagnostic approaches, as well as the emergence of drug-resistant forms of M. tuberculosis. Cellular immunity has a pivotal role against M. tuberculosis infection, but the role of humoral immunity is still controversial. We analyzed the frequency, absolute counts, and phenotypic and functional subsets of B lymphocytes in the peripheral blood of patients with active TB and subjects with latent infection compared to healthy donors. Moreover, we analyzed serum levels of total Ig and their IgA, IgM, and IgG isotypes and the titers of preexisting antibodies against a pool of common viral pathogens. FlowCT and unsupervised clusterization analysis show that patients with active TB and LTBI subjects have modest non-significant reduction in the numbers of circulating B lymphocytes as compared to healthy donors. Moreover, LTBI subjects had high percentages of atypical B cell population and lower percentages of naive and switched memory B cells. These findings were supported by gene expression and GSEA analysis. Moreover, there were no differences between active TB patients, LTBI subjects and HD, either in serum levels of total Ig isotypes or in preexisting IgG antibody titers, to ten different antigens from eight common pathogenic viruses, clearly demonstrating that either active or latent M. tuberculosis infection preserves the antibody production capacity of long-lived plasma cells. Thus, our results agree with previous studies reporting unaltered B cell frequencies in the blood of active TB patients and LTBI individuals as compared to healthy controls.

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Induction of Functional Specific Antibodies, IgG-Secreting Plasmablasts and Memory B Cells Following BCG Vaccination

Cited by 12 publications

References 85 publications

Evaluation of the consistence between the results of immunoinformatics predictions and real-world animal experiments of a new tuberculosis vaccine MP3RT

Evaluation of the consistence between the results of immunoinformatics predictions and real-world animal experiments of a new tuberculosis vaccine MP3RT

A century of BCG vaccination: Immune mechanisms, animal models, non-traditional routes and implications for COVID-19

Impact of Mycobacterium tuberculosis Infection on Human B Cell Compartment and Antibody Responses

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