# Cross development of surrogate efficacy mycobacterial growth inhibition assay endpoint for the translational guinea pig model

> **NIH NIH R03** · SEATTLE CHILDREN'S HOSPITAL · 2024 · $97,850

## Abstract

PROJECT SUMMARY AND ABSTRACT
Guinea pigs are an exceptional mid-pipeline model for evaluation of vaccine candidates against tuberculosis
(TB) disease. Guinea pigs develop the full range of pathological disease observed in humans, where mice do
not, and are still fairly simple to house unlike nonhuman primates. Unfortunately, unlike mice or nonhuman
primates the immunological reagents for guinea pig endpoints are widely underdeveloped or non-existent. There
is a gap in resources and endpoints for guinea pig research in the TB vaccine pipeline which limits their use.
Here we propose adopting and optimizing the peripheral blood monocyte cell (PBMC)-based mycobacterial
growth inhibition assay (MGIA) for use with guinea pig samples. The MGIA has been used for humans, mice and
nonhuman primates as a surrogate efficacy endpoint which evaluates the ability of PBMC from vaccinated
subjects to control mycobacteria ex vivo. To-date, the assay has not been evaluated using guinea pig samples.
Due to the relatively low number of cells required and elimination of the need for in vivo challenge this assay
affords a more high throughput evaluation of vaccine efficacy and addresses the 3Rs of animal research:
reduction, replacement, and refinement. PBMC and autologous serum samples have been collected from control
and vaccinated guinea pigs in historical studies which are available for this project. Using these available
samples allows a reduction in the need for live animals and helps make use of existing materials. The ex vivo
challenge of the MGIA replaces the need for in vivo challenge of live animals while also refining the endpoint.
Our colleagues at Oxford University have previously demonstrated that ex vivo efficacy correlates well with in
vivo challenge and subsequent bacterial control in preclinical models. We hypothesize that PBMC and serum
from bacillus Calmette–Guérin immunized guinea pigs will better control both bacillus Calmette–Guérin (BCG)
and Mycobacterium tuberculosis challenge in an ex vivo co-culture than non-immunized cohorts. Furthermore,
we expect that we will be able to identify the correct cell number and challenge dose to best resolve vaccine-
mediated differences. If successful, this optimized protocol would help align the preclinical pipeline efficacy
endpoints and provide a much needed tool for the guinea pig model. We will also make use of the co-culture
supernatants to evaluate the secreted effector molecules produced and look for differences between samples
that did or did not inhibit mycobacterial growth. Further mechanistic studies will explore the role of host cell
glycolytic metabolism on subsequent control. Together, this proposal aims to develop a new core methodology
for a highly translational animal model and begins to interrogate the mechanisms behind efficacy readouts.

## Key facts

- **NIH application ID:** 10786498
- **Project number:** 1R03AI180586-01
- **Recipient organization:** SEATTLE CHILDREN'S HOSPITAL
- **Principal Investigator:** Rhea N Coler
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $97,850
- **Award type:** 1
- **Project period:** 2024-05-16 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10786498

## Citation

> US National Institutes of Health, RePORTER application 10786498, Cross development of surrogate efficacy mycobacterial growth inhibition assay endpoint for the translational guinea pig model (1R03AI180586-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10786498. Licensed CC0.

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