Tuberculosis vaccination needs to avoid ‘decoy’ immune reactions

Iványi, Juraj

doi:10.1016/j.tube.2020.102021

Cited by 3 publications

(3 citation statements)

References 143 publications

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“…Despite lacking the region of difference 1 (RD1) ( 7 ), BCG contains several ‘decoy’ molecules, such as the glycoprotein LprG and Lipoarabinomannan (LAM), which evolved in support of virulence of mycobacteria. Both molecules delay the protective Th1 immune response via the induction of immunosuppressive cytokines and chemokines and could hence be counterproductive to prophylactic vaccination ( 54 , 55 ).…”

Section: Factors Associated With Vaccine Efficacy By Mucosal Deliverymentioning

confidence: 99%

Repurposing mucosal delivery devices for live attenuated tuberculosis vaccines

et al. 2023

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Tuberculosis (TB) remains one of the most lethal infectious diseases globally. The only TB vaccine approved by the World Health Organization, Bacille Calmette-Guérin (BCG), protects children against severe and disseminated TB but provides limited protection against pulmonary TB in adults. Although several vaccine candidates have been developed to prevent TB and are undergoing preclinical and clinical testing, BCG remains the gold standard. Currently, BCG is administered as an intradermal injection, particularly in TB endemic countries. However, mounting evidence from experimental animal and human studies indicates that delivering BCG directly into the lungs provides enhanced immune responses and greater protection against TB. Inhalation therapy using handheld delivery devices is used for some diseases and allows the delivery of drugs or vaccines directly into the human respiratory tract. Whether this mode of delivery could also be applicable for live attenuated bacterial vaccines such as BCG or other TB vaccine candidates remains unknown. Here we discuss how two existing inhalation devices, the mucosal atomization device (MAD) syringe, used for influenza vaccines, and the Respimat® Soft Mist™ inhaler, used for chronic obstructive pulmonary disease (COPD) therapy, could be repurposed for mucosal delivery of live attenuated TB vaccines. We also outline the challenges and outstanding research questions that will require further investigations to ensure usefulness of respiratory delivery devices that are cost-effective and accessible to lower- and middle-income TB endemic countries.

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Section: Factors Associated With Vaccine Efficacy By Mucosal Deliverymentioning

confidence: 99%

Repurposing mucosal delivery devices for live attenuated tuberculosis vaccines

et al. 2023

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“…Improving the magnitude and the quality of T cell responses that are specific to a single antigen by mucosal boosting may not be sufficient to stimulate significant additional protection to BCG. The responses to BCG vaccine are complex and it is possible that BCG could induce "decoy immune" responses to dominant BCG antigens that prevent the induction of preventive immune response to boosting vaccines [55]. Therefore, the selection of antigens for boosting vaccines is important, and could include M. tuberculosis proteins that are either missing from BCG or are non-dominant antigens in BCG.…”

Section: Plos Onementioning

confidence: 99%

Boosting BCG with recombinant influenza A virus tuberculosis vaccines increases pulmonary T cell responses but not protection against Mycobacterium tuberculosis infection

et al. 2021

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The current Mycobacterium bovis BCG vaccine provides inconsistent protection against pulmonary infection with Mycobacterium tuberculosis. Immunity induced by subcutaneous immunization with BCG wanes and does not promote early recruitment of T cell to the lungs after M. tuberculosis infection. Delivery of Tuberculosis (TB) vaccines to the lungs may increase and prolong immunity at the primary site of M. tuberculosis infection. Pulmonary immunization with recombinant influenza A viruses (rIAVs) expressing an immune-dominant M. tuberculosis CD4+ T cell epitope (PR8-p25 and X31-p25) stimulates protective immunity against lung TB infection. Here, we investigated the potential use of rIAVs to improve the efficacy of BCG using simultaneous immunization (SIM) and prime-boost strategies. SIM with parenteral BCG and intranasal PR8-p25 resulted in equivalent protection to BCG alone against early, acute and chronic M. tuberculosis infection. Boosting BCG with rIAVs increased the frequency of IFN-γ-secreting specific T cells (p<0.001) and polyfunctional CD4+ T cells (p<0.05) in the lungs compared to the BCG alone, however, this did not result in a significant increase in protection against M. tuberculosis compared to BCG alone. Therefore, sequential pulmonary immunization with these rIAVs after BCG increased M. tuberculosis-specific memory T cell responses in the lung, but not protection against M. tuberculosis infection.

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“…For the past approximately five decades, protective immunity was considered to be mediated by T cells, but the resulting extensive testing of cellular subsets (i.e., CD4, CD8, Th1/2, γδ, and Treg cells) and their cytokine products failed to identify a reliable test that correlated with protection following infection with Mycobacterium tuberculosis ( Mtb ) or vaccination. This failure could be attributed to immunoregulatory cytokines and to pathogenic “decoy” immune mechanisms induced by antigens, which have been evolved by the pathogen to evade host resistance [ 1 ].…”

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confidence: 99%