# Specific and Broadly Active Monoclonal Antibody Therapeutics Against The Filoviruses

> **NIH NIH U19** · LA JOLLA INSTITUTE FOR IMMUNOLOGY · 2021 · $2,222,178

## Abstract

Project 2: SUMMARY
The filoviruses, including multiple ebolaviruses and two marburgviruses, have emerged over 30 times to cause
outbreaks of severe disease with high mortality. The epidemic potential of these viruses is demonstrated by the
2013-2016 outbreak, which spread from a single infected toddler to 28,000 cases across multiple nations. No
therapeutic interventions are yet approved for filovirus infections, and there remains an urgent need for
efficacious treatments. In this academic and industry collaboration, we will advance both specific- and broadly
reactive monoclonal antibody (mAb) treatments that we have already shown to provide complete protection in
non-human primates. Importantly, this study builds upon results of a global collaboration, the Viral Hemorrhagic
Fever Immunotherapeutic Consortium (VIC), that yielded the most comprehensive dataset for anti-Ebola virus
mAbs yet assembled. From that comprehensive study, we learned additional correlates of mAb-mediated
protection and built improved, multivariate computational models, which predict treatment combinations that
maximize antibody features that most strongly predict in vivo protection (including Fc-mediated effector functions,
Fc glycoforms, and neutralization). Additional treatment combinations, one Ebola virus-specific and one broadly
cross-reactive, predicted by that detailed study may offer even greater efficacy than the two already in hand.
Using our therapeutic candidates and additional well-characterized VIC mAbs as controls, we will evaluate
thresholds of protection and correlates of protection across standard and innovative animal models. On a broader
level, this study will illuminate how faithfully particular mAb features (e.g., Fab-driven neutralization, species-
specific Fc-driven protection) translate across animal models used to satisfy the FDA “two-animal rule” for
therapeutic approval. We will further use innovative high-throughput technologies, standard cell-based assays,
targeted glycoforms and a library of well-characterized Fc substitutions to optimize both Fv and Fc to enhance
protective activity. For this project, we have engaged a multidisciplinary team of experts in structural biology,
virology, immunology, in vivo evaluation in animal models, computer modeling and statistical analysis, and
industrial mAb production and development. Our translational research program is informed by data that are
more comprehensive than any previously available, will forward optimized therapeutic candidates against
multiple viruses with epidemic potential, and will help establish a broadly applicable platform to treat filoviruses
and other infectious diseases.

## Key facts

- **NIH application ID:** 10158448
- **Project number:** 5U19AI142790-03
- **Recipient organization:** LA JOLLA INSTITUTE FOR IMMUNOLOGY
- **Principal Investigator:** Erica Ollmann Saphire
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $2,222,178
- **Award type:** 5
- **Project period:** 2019-05-01 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10158448

## Citation

> US National Institutes of Health, RePORTER application 10158448, Specific and Broadly Active Monoclonal Antibody Therapeutics Against The Filoviruses (5U19AI142790-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10158448. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*