The human antibody response to the surface of Mycobacterium tuberculosis.

Abstract

BACKGROUND: Vaccine-induced human antibodies to surface components of Haemophilus influenzae and Streptococcus pneumonia are correlated with protection. Monoclonal antibodies to surface components of Mycobacterium tuberculosis are also protective in animal models. We have characterized human antibodies that bind to the surface of live M. tuberculosis. METHODS: Plasma from humans with latent tuberculosis (TB) infection (n = 23), active TB disease (n = 40), and uninfected controls (n = 9) were assayed by ELISA for reactivity to the live M. tuberculosis surface and to inactivated M. tuberculosis fractions (whole cell lysate, lipoarabinomannan, cell wall, and secreted proteins). RESULTS: When compared to uninfected controls, patients with active TB disease had higher antibody titers to the surface of live M. tuberculosis (Δ = 0.72 log10), whole cell lysate (Δ = 0.82 log10), and secreted proteins (Δ = 0.62 log10), though there was substantial overlap between the two groups. Individuals with active disease had higher relative IgG avidity (Δ = 1.4 to 2.6) to all inactivated fractions. Surprisingly, the relative IgG avidity to the live M. tuberculosis surface was lower in the active disease group than in uninfected controls (Δ =  -1.53, p = 0.004). Patients with active disease had higher IgG than IgM titers for all inactivated fractions (ratios, 2.8 to 10.1), but equal IgG and IgM titers to the live M. tuberculosis surface (ratio, 1.1). Higher antibody titers to the M. tuberculosis surface were observed in active disease patients who were BCG-vaccinated (Δ = 0.55 log10, p = 0.008), foreign-born (Δ = 0.61 log10, p = 0.004), or HIV-seronegative (Δ = 0.60 log10, p = 0.04). Higher relative IgG avidity scores to the M. tuberculosis surface were also observed in active disease patients who were BCG-vaccinated (Δ = 1.12, p < 0.001) and foreign-born (Δ = 0.87, p = 0.01). CONCLUSIONS/SIGNIFICANCE: Humans with active TB disease produce antibodies to the surface of M. tuberculosis with low avidity and with a low IgG/IgM ratio. Highly-avid IgG antibodies to the M. tuberculosis surface may be an appropriate target for future TB vaccines.

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Citation

Published Version (Please cite this version)

10.1371/journal.pone.0098938

Publication Info

Perley, Casey C, Marc Frahm, Eva M Click, Karen M Dobos, Guido Ferrari, Jason E Stout and Richard Frothingham (2014). The human antibody response to the surface of Mycobacterium tuberculosis. PLoS One, 9(2). p. e98938. 10.1371/journal.pone.0098938 Retrieved from https://hdl.handle.net/10161/13898.

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Scholars@Duke

Ferrari

Guido Ferrari

Professor in Surgery

The activities of the Ferrari Laboratory are based on both independent basic research and immune monitoring studies. The research revolves around three main areas of interest: class I-mediated cytotoxic CD8+ T cell responses, antibody-dependent cellular cytotoxicity (ADCC), gene expression in NK and T cellular subsets upon infection with HIV-1. With continuous funding over the last 11 years from the NIH and Bill & Melinda Gates Foundation along with many other productive collaborations within and outside of Duke, the Ferrari Lab has expanded its focus of research to include the ontogeny of HIV-1 specific immune responses that work by eliminating HIV-1 infected cells and how these can be induced by AIDS vaccine candidates.

Stout

Jason Eric Stout

Professor of Medicine

My research focuses on the epidemiology, natural history, and treatment of tuberculosis and nontuberculous mycobacterial infections. I am also interested in the impact of HIV infection on mycobacterial infection and disease, and in examining health disparities as they relate to infectious diseases, particularly in immigrant populations.

Frothingham

Richard Frothingham

Associate Professor of Medicine

Dr. Frothingham is the principal investigator of a research laboratory which studies Mycobacterium tuberculosis, the cause of tuberculosis, and Mycobacterium avium, a closely related bacterium causing serious infections in AIDS patients. We are pursuing two current projects.

The first project aims to develop vaccines against M. avium and M. tuberculosis. We inject mice with candidate plasmid DNA vaccines which produce bacterial proteins in mouse muscle. We use a variety of DNA adjuvants to modify the immune response. We hope to use DNA vaccination to protect against new infections and to modify the course of existing infections. We also hope to identify correlates of vaccine-induced protective immunity.

The second project uses variations in bacterial DNA sequences to identify species and strains. Dr. Frothingham was part of a team of four Duke scientists who used DNA sequence analysis to identify the cause of Whipple's disease. He also identified used DNA sequence to identify a particular group of M. avium strains which cause disseminated infections in AIDS patients. We recently developed a new tuberculosis typing method using variable numbers of tandem DNA repeats. We are applying this new typing method in national and international collaborations.

Dr. Frothingham does not currently conduct clinical trials.

Special areas of expertise include tuberculosis, mycobacteria, strain differentiation, DNA vaccination, and pyrazinamide.

Key words: tuberculosis, mycobacteria, Mycobacterium tuberculosis, Mycobacterium avium, DNA vaccines, tandem repeat DNA, pyrazinamide, mouse


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