Evaluation of Humoral Immunity to Mycobacterium tuberculosis-Specific Antigens for Correlation with Clinical Status and Effective Vaccine Development.

Mamiko Niki,Yukihiro Kaneko,Sohkichi Matsumoto,Atsuyuki Kurashima,Kozo Morimoto,Hideaki Nagai,Yoshihiko Hoshino,Shunsuke Akashi,Manabu Inoue,Seigo Kitada,Ken Ohta,Maho Suzukawa,Koichi Suzuki,Makoto Niki

doi:10.1155/2015/527395

Abstract

Although tuberculosis remains a major global health problem, Bacille Calmette-Guérin (BCG) is the only available vaccine. However, BCG has limited applications, and a more effective vaccine is needed. Cellular mediated immunity (CMI) is thought to be the most important immune response for protection against Mycobacterium tuberculosis (Mtb). However, the recent failure of a clinical trial for a booster BCG vaccine and increasing evidence of antibody-mediated immunity prompted us to evaluate humoral immunity to Mtb-specific antigens. Using Enzyme-Linked ImmunoSpot and Enzyme-Linked ImmunoSorbent Assays, we observed less correlation of both CMI and IgG titers with patient clinical status, including serum concentration of C reactive protein. However, IgA titers against Mtb were significantly correlated with clinical status, suggesting that specific IgA antibodies protect against Mtb proliferation. In addition, in some cases, IgA antibody titers were significantly associated with the serum concentration of total albumin, which supports the idea that humoral immunity can be influenced by the nutritional status. Based on these observations, we propose that the induction of humoral immunity should be included as an option in TB vaccine development strategies.

Highlights

Tuberculosis (TB) remains a leading cause of death in many regions of the world and one-third of the world’s population is thought to be asymptomatic carriers of the causative agent, Mycobacterium tuberculosis (Mtb)
Titers of IgG and IgA antibodies against recombinant mycobacterial antigens were measured separately in the sera of “Active disease” (n = 88), “Past disease” (n = 84), Latent TB infection (LTBI) (n = 18) cases, and control (n = 77)
We chose mycobacteria-specific antigens based on (1) proteome analysis of antibody responses to Mtb from active TB patients [25, 26]; (2) in silico studies performed to identify TB vaccine candidates [27]; and (3) publications identifying heparin-binding haemagglutinin adhesin (HBHA) and mycobacterial DNA-binding protein 1 (MDP1) as mycobacteriaspecific antigens [22, 28, 29]

Summary

Introduction

Tuberculosis (TB) remains a leading cause of death in many regions of the world and one-third of the world’s population is thought to be asymptomatic carriers of the causative agent, Mycobacterium tuberculosis (Mtb). Recent progress in methods of vaccine development has been covered in several excellent reviews and will not be addressed here [4, 5] The majority of these candidate vaccines focus on improving cell-mediated immunity (CMI) to Mtb by modifying the current BCG platform or boosting BCG with a different format, and some candidate vaccines. Two ongoing vaccine trials for the fungus Candida albicans, a major human pathogen, are expected to transduce protection by inducing antibody-mediated immunity [16]. These studies suggest that humoral immunity might play an important role in protection against Mtb infection, a function which could be used to develop a new technology for more effective vaccine development. The results suggest that IgA antibodies against Mtb components would make suitable Mtb vaccine candidates

Subjects and Methods

Results

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Conflict of Interests