Antibody-mediated immunity against tuberculosis: implications for vaccine development

Abstract

There is an urgent need for new and better vaccines against tuberculosis (TB). Current vaccine design strategies are generally focused on the enhancement of cell-mediated immunity. Antibody-based approaches are not being considered, mostly due to the paradigm that humoral immunity plays little role in the protection against intracellular pathogens. Here, we reappraise and update the increasing evidence for antibody-mediated immunity against Mycobacterium tuberculosis, discuss the complexity of antibody responses to mycobacteria, and address mechanism of protection. Based on these findings and discussions, we challenge the common belief that immunity against M. tuberculosis relies solely on cellular defense mechanisms, and posit that induction of antibody-mediated immunity should be included in TB vaccine development strategies.

Figure 1. Interpretation of the Potential Function of Pro- and Anti-Inflammatory Antibodies against M.tb in the Context of the Damage-Response Framework by Casadevall and Pirofski

(A) Potential effects of a proinflammatory antibody with enhanced inflammation leading on the one hand to the improvement from disseminated/miliary TB in an immunocompromised host (left) to localized granuloma formation, and on the other hand to progression from granuloma to caseous necrosis in the more immunocompetent host (right). (B) Potential effects of an anti-inflammatory antibody leading to worsening TB dissemination in the immunocompromised host who has already reduced inflammation (left), but improved containment of local disease from caseous necrosis to granuloma formation in the more immunocompetent host with a strong inflammatory response (right). LTBI, latent TB infection.