A general method for characterization of humoral immunity induced by a vaccine or infection

Legutki, Joseph Barten; Magee, D. Mitchell; Stafford, Phillip; Johnston, Stephen Albert

doi:10.1016/j.vaccine.2010.04.061

Cited by 73 publications

(85 citation statements)

References 22 publications

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“…Immunosignaturing is well-suited for detection and classification of diseases and vaccines (4,5,(22)(23)(24)(25)(26). In each of these demonstrations, there were controls representing an "unaffected" state, but the clinical definition of unaffected varied by researcher.…”

Section: Discussionmentioning

confidence: 99%

General Assessment of Humoral Activity in Healthy Humans

Stafford

Wrapp

Johnston

2016

Molecular & Cellular Proteomics

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The humoral immune system is network of biological molecules designed to maintain a healthy homeostatic equilibrium. Because antibodies are an abundant and highly specific effector of immunological action, they are also an important reservoir of previous host exposures. Antibodies may play a major role in early detection of host challenge. Unfortunately, few practical methods exist for interpreting the information stored in antibody variable regions. Immunosignatures use a microarray of thousands of random sequence peptides to interrogate antibodies in a broad and unbiased fashion. The pattern of binding between antibody and peptide is reproducible. Once the system has been trained on a disease cohort, blinded samples can be reliably predicted. Although immunosignatures of both chronic and infectious disease have been extensively tested, less has been done to demonstrate how healthy immunosignatures change over time or between individuals. Here, we report the results of a study of immunosignatures of healthy persons over brief (12 h sampled once per hour), intermediate (32 days sampled once per day), and long (5 years sampled once every year) time spans. Using this information, we were also able to detect intentional and unintentional immunological perturbations in the form of a vaccine and an infection, respectively. Our findings suggest that, even with the variability inherent in healthy immunosignatures, a single person's immunosignature will remain constant over time. Over this healthy signature, vaccines and infections create subsignatures that are common across multiple people, even subsuming healthy fluctuations.

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Section: Discussionmentioning

confidence: 99%

General Assessment of Humoral Activity in Healthy Humans

Stafford

Wrapp

Johnston

2016

Molecular & Cellular Proteomics

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“…The blood is diluted with little or no additional processing and incubated with a large array of different nonnatural-sequence peptides (reviewed in Sykes et al 9 ). Our initial platform was an array of 10,000 presynthesized peptides spotted on a glass slide, and we have used this format to characterize immune responses to vaccines 10 , infectious diseases 11 , cancer 12,13 , Alzheimer's Disease 14 and autoimmune disorders 12 . The work on brain cancer 13 was performed as a blinded train/test study, training on a patient cohort taken in 2007 and testing on a cohort from 2010, with 100% accuracy of identification.…”

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confidence: 99%

Scalable high-density peptide arrays for comprehensive health monitoring

Legutki

Zhao

Greving³

et al. 2014

Nat Commun

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“…The 10,000-nonnatural sequence peptide immunosignature array and the 96-peptide VF diagnostic arrays were produced and processed as described in Legutki et al (13,19). Briefly, the peptides were spotted onto standard slides using a noncontact Piezo printer.…”

Section: Methodsmentioning

confidence: 99%

“…As noted, the most clinically pressing issue is the low sensitivities of these diagnostics as primary tests. We propose utilizing the immunosignature diagnostic technology (13) to address some or all of the limitations of current diagnostics for VF, particularly as a diagnosis for patients misclas-sified at the first test. The immunosignature technology utilizes a high-density array of non-life-space peptides to provide mimics of epitopes, even those that are discontinuous or nonproteins.…”

Section: Occidioidomycosis Commonly Known As Valley Fever (Vf) Ismentioning

confidence: 99%

“…An immunosignature, unlike many genetic or immunological tests, is both sample sparing and robust to sample handling (14). Because the sensitivity of an immunosignature is higher than that of ELISA-based serological tests (13,15), and discrimination across multiple diseases is possible, we asked whether the platform was suited to be used as a valley fever diagnostic method both for diagnosing VF and differentiating between other common respiratory infections. Current VF diagnostic methods may produce false-negative results, resulting in late recognition of the disease (16)(17)(18), which adversely affects patient outcomes.…”

Section: Occidioidomycosis Commonly Known As Valley Fever (Vf) Ismentioning

confidence: 99%

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Application of Immunosignatures for Diagnosis of Valley Fever

Navalkar

Johnston

Woodbury

et al. 2014

Clin. Vaccine Immunol.

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Valley fever (VF) is difficult to diagnose, partly because the symptoms of VF are confounded with those of other communityacquired pneumonias. Confirmatory diagnostics detect IgM and IgG antibodies against coccidioidal antigens via immunodiffusion (ID). The false-negative rate can be as high as 50% to 70%, with 5% of symptomatic patients never showing detectable antibody levels. In this study, we tested whether the immunosignature diagnostic can resolve VF false negatives. An immunosignature is the pattern of antibody binding to random-sequence peptides on a peptide microarray. A 10,000-peptide microarray was first used to determine whether valley fever patients can be distinguished from 3 other cohorts with similar infections. After determining the VF-specific peptides, a small 96-peptide diagnostic array was created and tested. The performances of the 10,000-peptide array and the 96-peptide diagnostic array were compared to that of the ID diagnostic standard. The 10,000-peptide microarray classified the VF samples from the other 3 infections with 98% accuracy. It also classified VF falsenegative patients with 100% sensitivity in a blinded test set versus 28% sensitivity for ID. The immunosignature microarray has potential for simultaneously distinguishing valley fever patients from those with other fungal or bacterial infections. The same 10,000-peptide array can diagnose VF false-negative patients with 100% sensitivity. The smaller 96-peptide diagnostic array was less specific for diagnosing false negatives. We conclude that the performance of the immunosignature diagnostic exceeds that of the existing standard, and the immunosignature can distinguish related infections and might be used in lieu of existing diagnostics.

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A general method for characterization of humoral immunity induced by a vaccine or infection

Cited by 73 publications

References 22 publications

General Assessment of Humoral Activity in Healthy Humans

General Assessment of Humoral Activity in Healthy Humans

Scalable high-density peptide arrays for comprehensive health monitoring

Application of Immunosignatures for Diagnosis of Valley Fever

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