ArticlePloS one2013
Vaccination with recombinant Mycobacterium tuberculosis PknD attenuates bacterial dissemination to the brain in guinea pigs.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed.
- Central Nervous System Tuberculosis in a Murine Model: Neurotropic Strains or a New Pathway of Infection?Pathogens (Basel, Switzerland) · 2023Article
- Controlled Human Infection Models To Accelerate Vaccine Development.Clinical microbiology reviews · 2022Review
- Review
- Mycobacteria employ two different mechanisms to cross the blood-brain barrier.Cellular microbiology · 2018Article
- Tuberculous meningitis: a roadmap for advancing basic and translational research.Nature immunology · 2018Article
- Large-scale genomic analysis shows association between homoplastic genetic variation in Mycobacterium tuberculosis genes and meningeal or pulmonary tuberculosis.BMC genomics · 2018Article
- Pan-Genomic Study ofFrontiers in microbiology · 2018Article
- Modelling of cerebral tuberculosis in BALB/c mice using clinical strain from patients with CNS tuberculosis infection.The Indian journal of medical research · 2017Article
- Article
- Article
- Mycobacterium tuberculosis pellicles express unique proteins recognized by the host humoral response.Pathogens and disease · 2014Article
- Novel vaccine strategies against tuberculosis: a road less travelled.Expert review of vaccines · 2013Article
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Authors and funding
7 authors.
Funding
Abstract
backgroundWe have previously identified Mycobacterium tuberculosis PknD to be an important virulence factor required for the pathogenesis of central nervous system (CNS) tuberculosis (TB). Specifically, PknD mediates bacillary invasion of the blood-brain barrier, which can be neutralized by specific antisera, suggesting its potential role as a therapeutic target against TB meningitis. METHODOLOGY/PRINCIPAL
findingsWe utilized an aerosol challenge guinea pig model of CNS TB and compared the protective efficacy of recombinant M. tuberculosis PknD subunit protein with that of M. bovis BCG against bacillary dissemination to the brain. BCG vaccination limited the pulmonary bacillary burden after aerosol challenge with virulent M. tuberculosis in guinea pigs and also reduced bacillary dissemination to the brain (P = 0.01). PknD vaccination also offered significant protection against bacterial dissemination to the brain, which was no different from BCG (P>0.24), even though PknD vaccinated animals had almost 100-fold higher pulmonary bacterial burdens. Higher levels of PknD-specific IgG were noted in animals immunized with PknD, but not in BCG-vaccinated or control animals. Furthermore, pre-incubation of M. tuberculosis with sera from PknD-vaccinated animals, but not with sera from BCG-vaccinated or control animals, significantly reduced bacterial invasion in a human blood-brain barrier model (P<0.01).
conclusionCurrent recommendations for administering BCG at birth are based on protection gained against severe disease, such as TB meningitis, during infancy. We demonstrate that vaccination with recombinant M. tuberculosis PknD subunit offers a novel strategy to protect against TB meningitis, which is equivalent to BCG in a guinea pig model. Moreover, since BCG lacks the PknD sensor, BCG could also be boosted to develop a more effective vaccine against TB meningitis, a devastating disease that disproportionately affects young children.
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