# Enhanced POC assay for TB in HIV-infected children based on the ultrasensitive detection of the urinary form of the lipoarabinomannan antigen

> **NIH NIH R01** · RBHS-NEW JERSEY MEDICAL SCHOOL · 2021 · $747,759

## Abstract

Abstract
TB remains a major source of mortality in young children in endemic areas, particularly in areas where there is
a high rate of HIV infection. These children are difficult to diagnose with existing assays, and it is believed that
many of the >230,000 children who died because of TB in 2017 could have been saved with better diagnostics.
A highly promising biomarker for diagnosing TB is lipoarabinomannan (LAM), a major mycobacterial surface
glyolipid that accumulates at different concentrations in the great majority of actively infected TB patients. Our
lab has recently made major contributions towards understanding the diversity of the antigenic properties of
LAM and the complexity of the humoral immune rsponse against this antigen. One surprising discovery
resulting from our work is that the urinary form of TB LAM (uLAM) is antigenically distinct from the bacterially
associated form (ManLAM), and we have identified novel combinations of monoclonal antibodies that allow the
sensitive and specific detection of uLAM. This has recently led to the production of a new lateral flow assay
(the Fujifilm SILVAMP TB LAM assay) that has a significantly increased sensitivity for uLAM over that of the
commercial assay. However, despite this improvement, the sensitivity and robustness of this assay is still not
sufficient to meet the WHO requirements for an optimal assay. This proposal will build on our previous work to
further improve the affinities and specificities of our existing reagents, and identify new reagents with increased
sensitivity and accuracy for uLAM. To better understand the nature of uLAM and provide standardized samples
for future assays we will solate large volumes (~ 2L) of urine from positive patients with a range of uLAM levels,
and freeze away multiple aliquots of these samples for future use. A selected set of these urines will be used to
purify high concentrations of uLAM from multiple patients, and the structural and immunological properties of
these antigens will be compared. We have engineered forms of existing capture and detection reagents that
have improved affinities/avidities for ManLAM, and the sensitivity of these reagents will be compared to those
of existing reagents and lateral flow assays against several cohorts of pediatric urine samples that meet the
requirements of this RFA (<5 years old, >20% HIV+). We will screen memory B cell populations from selected
patients to identify new mabs with high affinities and/or specificities for uLAM, and select yeast display libraries
generated by randomization of the key CDR regions of our lead detection reagent for variants with higher
affinities and specificites than the parental antibody. The binding properties of these new mAbs will be
characterized, and their efficacy in detecting uLAM in the pediatric samples will be tested. Antibody
combinations with demonstrably better sensitivities than existing reagents will be transferred to our commercial
collaborators at Fujifil...

## Key facts

- **NIH application ID:** 10144934
- **Project number:** 5R01AI152157-02
- **Recipient organization:** RBHS-NEW JERSEY MEDICAL SCHOOL
- **Principal Investigator:** ABRAHAM PINTER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $747,759
- **Award type:** 5
- **Project period:** 2020-04-14 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10144934

## Citation

> US National Institutes of Health, RePORTER application 10144934, Enhanced POC assay for TB in HIV-infected children based on the ultrasensitive detection of the urinary form of the lipoarabinomannan antigen (5R01AI152157-02). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10144934. Licensed CC0.

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