The human antibody response to the surface of Mycobacterium tuberculosis.

Perley, Casey C

Frahm, Marc

Click, Eva M

Dobos, Karen M

Ferrari, Guido

Stout, Jason E

Frothingham, Richard

Pai, Madhukar

United States

2017-04-01T13:19:36Z

2017-04-01T13:19:36Z

2014

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.

https://www.ncbi.nlm.nih.gov/pubmed/24918450

PONE-D-14-16147

1932-6203

https://hdl.handle.net/10161/13898

eng

Public Library of Science (PLoS)

PLoS One

10.1371/journal.pone.0098938

Adult

Antibodies, Bacterial

Antibody Affinity

Antibody Formation

Female

Humans

Immunoglobulin G

Immunoglobulin M

Latent Tuberculosis

Male

Middle Aged

Mycobacterium tuberculosis

Tuberculosis

Young Adult

The human antibody response to the surface of Mycobacterium tuberculosis.

Journal article

Ferrari, Guido|0000-0001-7747-3349

Stout, Jason E|0000-0002-6698-8176

https://www.ncbi.nlm.nih.gov/pubmed/24918450

e98938

2

Basic Science Departments

Clinical Science Departments

Duke

Duke Human Vaccine Institute

Global Health Institute

Institutes and Centers

Institutes and Provost's Academic Units

Medicine

Medicine, Duke Human Vaccine Institute

Medicine, Infectious Diseases

Molecular Genetics and Microbiology

School of Medicine

Surgery

Surgery, Surgical Sciences

University Institutes and Centers

Published online

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