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Tools to therapeutically harness the human antibody response.

ABSTRACT: The natural human antibody response is a rich source of highly specific, neutralizing and self-tolerant therapeutic reagents. Recent advances have been made in isolating and characterizing monoclonal antibodies that are generated in response to natural infection or vaccination. Studies of the human antibody response have led to the discovery of crucial epitopes that could serve as new targets in vaccine design and in the creation of potentially powerful immunotherapies. With a focus on influenza virus and HIV, herein we summarize the technological tools used to identify and characterize human monoclonal antibodies and describe how these tools might be used to fight infectious diseases.

SUBMITTER: Wilson PC

PROVIDER: S-EPMC7097371 | biostudies-literature | 2012 Oct

REPOSITORIES: biostudies-literature

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Tools to therapeutically harness the human antibody response.

Wilson Patrick C PC Andrews Sarah F SF

Nature reviews. Immunology 20121001 10

The natural human antibody response is a rich source of highly specific, neutralizing and self-tolerant therapeutic reagents. Recent advances have been made in isolating and characterizing monoclonal antibodies that are generated in response to natural infection or vaccination. Studies of the human antibody response have led to the discovery of crucial epitopes that could serve as new targets in vaccine design and in the creation of potentially powerful immunotherapies. With a focus on influenza ...[more]

PMID: 23007571

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Project description:BackgroundVaccine-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.MethodsPlasma 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).ResultsWhen compared to uninfected controls, patients with active TB disease had higher antibody titers to the surface of live M. tuberculosis (? = 0.72 log10), whole cell lysate (? = 0.82 log10), and secreted proteins (? = 0.62 log10), though there was substantial overlap between the two groups. Individuals with active disease had higher relative IgG avidity (? = 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 (? =? -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 (? = 0.55 log10, p = 0.008), foreign-born (? = 0.61 log10, p = 0.004), or HIV-seronegative (? = 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 (? = 1.12, p < 0.001) and foreign-born (? = 0.87, p = 0.01).Conclusions/significanceHumans 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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Tools to therapeutically harness the human antibody response.

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Tools to therapeutically harness the human antibody response.

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