Abstract
Protein aggregates have been reported to act as a reservoir that can release biologically active, native form of precursor protein. Keeping this fact into consideration, it is tempting to exploit protein aggregate-based antigen delivery system as a functional vaccine to expand desirable immunological response in the host. Herein, we explored the capacity of aggregated Ag85B of Mycobacterium tuberculosis (Mtb) to act as a prophylactic vaccine system that releases the precursor antigen in slow and sustained manner. Being particulate system with exposed hydrophobic residues, aggregated Ag85B is likely to be avidly taken up by both phagocytosis as well as fusion with plasma membrane of antigen presenting cells, leading to its direct delivery to their cytosol. Its unique ability to access cytosol of target cells is further evident from the fact that immunization with aggregated Ag85B led to the induction of Th1-dominant immune response along with upregulated expression of qualitatively superior polyfunctional T cells in the mice. Antibodies generated following immunization with aggregated antigen recognized both native and monomeric Ag85B released from protein aggregate. The implicated immunization strategy offers protection at par to that of established BCG vaccine with desirable central and effector memory responses against subsequent Mtb aerosol challenge. The study highlights the potential of aggregated Ag85B as promising antigen delivery system and paves the way to design better prophylactic regimes against various intracellular pathogens including Mtb.
Highlights
Tuberculosis (TB) is a major global health problem affecting over one-third population of the world
Ag85B protein aggregates obtained by continuous agitation for 24 h were evaluated for presence of amyloid specific signature peak shift employing Congo Red (CR) binding assay
The data were analyzed by employing two-way ANOVA followed by Bonferroni’s multiple comparison test and are shown as the means (±SEM) of three independent determinants where; p < 0.05(*), p < 0.01(**), and p < 0.001(***) were considered significant
Summary
Tuberculosis (TB) is a major global health problem affecting over one-third population of the world. Around 10–15% of the subjects exposed to Mycobacterium tuberculosis (Mtb) develop active disease, while remaining may act as a carrier of latent form of the infection [1]. Amyloid Based Vaccine Against Tuberculosis subjects who are on immuno-suppression therapy (cf., post organ transplantation) or having co-infection with HIV and other immune-associated complications are more susceptible to full blown TB infection. The emergence of MDR/XDR isolates against available anti-TB antibiotics has further complicated the situation. Bacillus Calmette–Guerin (BCG), the only approved vaccine against TB offers promising prophylaxis against childhood miliary TB, remain capricious in providing protection to immunized adults. Despite the admittance of at least 13 potential vaccine candidates in various developmental stages of clinical trials to replace BCG, TB vaccine discovery program is still bleak and necessitates conceptual rejuvenation [2]
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