Novel Vaccination Strategies against Tuberculosis

Abstract

The tuberculosis (TB) pandemic continues to rampage despite widespread use of the BCG (Bacillus Calmette -Guérin) vaccine. Novel vaccination strategies are urgently needed to arrest global transmission and prevent the uncontrolled development of multidrug-resistant forms of Mycobacterium tuberculosis. Over the last two decades, considerable progress has been made in the field of vaccine development with numerous innovative preclinical candidates and more than a dozen vaccines in clinical trials. These vaccines are developed either as boosters of the current BCG vaccine or as novel prime vaccines to replace BCG. Given the enormous prevalence of latent TB infection, vaccines that are protective on top of an already established infection remain a high priority and a significant scientific challenge. Here we discuss the current state of TB vaccine research and development, our understanding of the underlying immunology, and the requirements for an efficient TB vaccine.

Mycobacterial L-forms are found in cord blood: A potential vertical transmission of BCG from vaccinated mothers

“…10 The maintenance of specific immunity necessarily needs BCG bacilli to produce immunogenic substances, associated mainly with cell wall compounds. 12 Our last study confirmed that live mycobacterial L-forms persist in the blood of BCG vaccinated people. Forty five of 97 genetically tested blood cultures were identified as L-forms of mycobacteria belonging to Mycobacterium tuberculosis complex.…”

Absolute Proteome Composition and Dynamics during Dormancy and Resuscitation of Mycobacterium tuberculosis

“…Moreover, knowledge of absolute protein concentrations might help to prioritize immune-dominant target antigens of the human T cell response for subunit vaccines against tuberculosis. To prevent disease outbreak in individuals with latent tuberculosis, emphasis is now given to so-called multi-stage vaccines that express both antigens of dormant and replicating bacilli (Andersen and Kaufmann, 2014). The here-described method and resulting resource of Mtb protein concentrations during dormancy and resuscitation will facilitate identification of appropriate antigens for rational design of future multi-stage vaccines.…”

Immune Response to Tuberculosis as a Basis for Rational Vaccination Strategies

“…Strategies at Level 1.0 take advantage of a prime vaccination with conventional BCG to strengthen the immune response by booster with a subunit vaccine ( [50][51][52]. These are composed either of a dominant protein antigen formulated in an adjuvant, which stimulates T cells efficiently, or is expressed by a recombinant viral carrier [53]. None of these vaccine candidates induces protection at a level better than BCG in preclinical models, but all increase the protective efficacy caused by a BCG prime.…”