Host immune responses to mycobacterial antigens and their implications for the development of a vaccine to control tuberculosis

Yuk, Jae–Min; Jo, Eun‐Kyeong

doi:10.7774/cevr.2014.3.2.155

Cited by 43 publications

(36 citation statements)

References 132 publications

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“…The current, commercially available, BCG vaccine is associated with variable effectiveness against Mtb infection and disease, and is not indicated for immunocompromised individuals [108–110] . Testing new TB vaccines in NHP models is of considerable interest, to optimize schedule and administration regimens, as well as comparison of different adjuvant and delivery strategies.…”

Section: Discussionmentioning

confidence: 99%

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The TB-specific CD4+ T cell immune repertoire in both cynomolgus and rhesus macaques largely overlap with humans

et al. 2015

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Summary Non-human primate (NHP) models of tuberculosis (TB) immunity and pathogenesis, especially rhesus and cynomolgus macaques, are particularly attractive because of the high similarity of the human and macaque immune systems. However, little is known about the MHC class II epitopes recognized in macaques, thus hindering the establishment of immune correlates of immunopathology and protective vaccination. We characterized immune responses in rhesus macaques vaccinated against and/or infected with Mycobacterium tuberculosis (Mtb), to a panel of antigens currently in human vaccine trials. We defined 54 new immunodominant CD4+ T cell epitopes, and noted that antigens immunodominant in humans are also immunodominant in rhesus macaques, including Rv3875 (ESAT-6) and Rv3874 (CFP10). Pedigree and inferred restriction analysis demonstrated that this phenomenon was not due to common ancestry or inbreeding, but rather presentation by common alleles, as well as, promiscuous binding. Experiments using a second cohort of rhesus macaques demonstrated that a pool of epitopes defined in the previous experiments can be used to detect T cell responses in over 75% of individual monkeys. Additionally, 100% of cynomolgus macaques, irrespective of their latent or active TB status, responded to rhesus and human defined epitope pools. Thus, these findings reveal an unexpected general repertoire overlap between MHC class II epitopes recognized in both species of macaques and in humans, showing that epitope pools defined in humans can also be used to characterize macaque responses, despite differences in species and antigen exposure. The results have general implications for the evaluation of new vaccines and diagnostics in NHPs, and immediate applicability in the setting of macaque models of TB.

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Section: Discussionmentioning

confidence: 99%

“…Several Mtb antigens immunodominant in humans [81–83,103,110,116–120] are included in the design of new TB vaccines. Herein, we tested the immunogenicity in rhesus macaques of a set of antigens that have been used in human clinical trials and diagnostics.…”

Section: Discussionmentioning

confidence: 99%

The TB-specific CD4+ T cell immune repertoire in both cynomolgus and rhesus macaques largely overlap with humans

et al. 2015

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“…After Mtb is inhaled and transmitted to the lungs, it is phagocytized by alveolar macrophages and eliminated by various mechanisms (Yuk & Jo, 2014). The ability of Mtb to survive within macrophages is an important determinant of the outcome of infection.…”

Section: Mtb Infection Of Alveolar Macrophages and Alveolar Epithementioning

confidence: 99%

“…The ability of Mtb to survive within macrophages is an important determinant of the outcome of infection. If the host fails in eradicating the bacteria, the disease is preserved in a latent condition, which can either be terminated with an appropriate host innate immune response or lead to Mtb replication in macrophages and dissemination to other tissues (Yuk & Jo, 2014). Mtb primarily escapes eradication by impairing phagosome maturation (Gengenbacher & Kaufmann, 2012).…”

Section: Mtb Infection Of Alveolar Macrophages and Alveolar Epithementioning

confidence: 99%

The microbiome at the pulmonary alveolar niche and its role in Mycobacterium tuberculosis infection

Adami

Cervantes

2015

Tuberculosis

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Advances in next generation sequencing (NGS) technology have provided the tools to comprehensively and accurately characterize the microbial community in the respiratory tract in health and disease. The presence of commensal and pathogenic bacteria has been found to have important effects on the lung immune system. Until relatively recently, the lung has received less attention compared to other body sites in terms of microbiome characterization, and its study carries special technological difficulties related to obtaining reliable samples as compared to other body niches. Additionally, the complexity of the alveolar immune system, and its interactions with the lung microbiome, are only just beginning to be understood. Amidst this complexity sits Mycobacterium tuberculosis (Mtb), one of humanity’s oldest nemeses and a significant public health concern, with millions of individuals infected with Mtb worldwide. The intricate interactions between Mtb, the lung microbiome, and the alveolar immune system are beginning to be understood, and it is increasingly apparent that improved treatment of Mtb will only come through deep understanding of the interplay between these three forces. In this review, we summarize our current understanding of the lung microbiome, alveolar immunity, and the interaction of each with Mtb.

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“…tuberculosis secretory proteins, such as Ag85A and ESAT-6, are considered to be important protective antigens in TB vaccine design [12]. Based on this, we generated several DNA vaccines encoding these antigens and showed enhanced humoral immunity and therapeutic efficacy in mice and non-human primate models [13][14][15][16].…”

Section: Introductionmentioning

confidence: 99%

Boosting BCG-primed mice with chimeric DNA vaccine HG856A induces potent multifunctional T cell responses and enhanced protection against Mycobacterium tuberculosis

Kang

et al. 2015

Immunol Res

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The tuberculosis pandemic continues to rampage despite widespread use of the current Bacillus Calmette-Guerin (BCG) vaccine. Because DNA vaccines can elicit effective antigen-specific immune responses, including potent T cell-mediated immunity, they are promising vehicles for antigen delivery. In a prime-boost approach, they can supplement the inadequate anti-TB immunological memory induced by BCG. Based on this, a chimeric DNA vaccine HG856A encoding Mycobacterium tuberculosis (M. tuberculosis) immunodominant antigen Ag85A plus two copies of ESAT-6 was constructed. Potent humoral immune responses, as well as therapeutic effects induced by this DNA vaccine, were observed previously in M. tuberculosis-infected mice. In this study, we further evaluated the antigen-specific T cell immune responses and showed that repeated immunization with HG856A gave modest protection against M. tuberculosis challenge infection and significantly boosted the immune protection primed by BCG vaccination. Enhanced protection was accompanied by increased multifunctional Th1 CD4(+) T cell responses, most notably by an elevated frequency of M. tuberculosis antigen-specific IL-2-producing CD4(+) T cells post-vaccination. These data confirm the potential of chimeric DNA vaccine HG856A as an anti-TB vaccine candidate.

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Host immune responses to mycobacterial antigens and their implications for the development of a vaccine to control tuberculosis

Cited by 43 publications

References 132 publications

The TB-specific CD4+ T cell immune repertoire in both cynomolgus and rhesus macaques largely overlap with humans

The TB-specific CD4+ T cell immune repertoire in both cynomolgus and rhesus macaques largely overlap with humans

The microbiome at the pulmonary alveolar niche and its role in Mycobacterium tuberculosis infection

Boosting BCG-primed mice with chimeric DNA vaccine HG856A induces potent multifunctional T cell responses and enhanced protection against Mycobacterium tuberculosis

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