# Eliciting and isolating neutralizing antibodies against Powassan virus

> **NIH NIH R21** · ALBERT EINSTEIN COLLEGE OF MEDICINE · 2022 · $210,000

## Abstract

SUMMARY
Powassan virus (POWV) is a tick-disseminated flavivirus that causes severe encephalitis, meningitis, and
long-term neurological damage. Although POWV infections are relatively rare, the virus is widely distributed
among common vectors such as Ixodes scapularis (the deer tick) and the number of reported cases in the
US is rising each year. There are no approved vaccines or treatments for POWV infection. The goals of this
R21 proposal are two-fold. In Aim 1, we will investigate the potential of protein nanoparticle immunogens
bearing recombinantly-expressed POWV glycoprotein E domain III (EDIII) to induce neutralizing antibody
response in mice. EDIII is an attractive target for flavivirus subunit vaccine design because it is relatively
small (~80 residues) and contains epitopes of protective antibodies against multiple flaviviruses such as
Dengue virus (DENV), Zika virus (ZIKV), West Nile virus (WNV), and Looping Ill virus (LIV). However, EDIII
as a monomer is poorly immunogenic because it lacks the capacity to crosslink surface B-cell receptors
(BCRs) to stimulate a robust antibody response. This limitation can be overcome by presenting EDIII in
multivalent format as part of a protein nanoparticle. We have generated a prototypic POWV EDIII
nanoparticle vaccine using Spycatcher/Spytag conjugation technology, and pilot studies have demonstrated
this nanoparticle can elicit neutralizing antibodies in mice. We will further optimize this and related POWV
nanoparticle vaccines. In Aim 2, we will isolate a large panel of human monoclonal antibodies (hu-mAbs)
from a living survivor of POWV infection by single B cell sorting. Hu-mAbs have strong potential as
immunotherapies because they are highly specific and their human scaffold minimizes the risk for anti-drug
antibody responses. Furthermore, profiling hu-mAbs provides direct information about human immune
response that can then be used to inform vaccine design. We will test the POWV hu-mAbs for their capacity
to bind POWV E and neutralize POWV reporter virus particles (RVPs). This work will provide new insights
and candidates for prevention and treatment of POWV infection.

## Key facts

- **NIH application ID:** 10459523
- **Project number:** 5R21AI164049-02
- **Recipient organization:** ALBERT EINSTEIN COLLEGE OF MEDICINE
- **Principal Investigator:** Jonathan R. Lai
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $210,000
- **Award type:** 5
- **Project period:** 2021-08-01 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10459523

## Citation

> US National Institutes of Health, RePORTER application 10459523, Eliciting and isolating neutralizing antibodies against Powassan virus (5R21AI164049-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10459523. Licensed CC0.

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