# The first polymeric opioid conjugate vaccine

> **NIH NIH R21** · JOHNS HOPKINS UNIVERSITY · 2021 · $204,688

## Abstract

1. Abstract:
Opioid addiction is a national medical crisis that is expected to worsen due to the socioeconomic fallout caused by the
SARS-CoV-2 pandemic. Opioid vaccines are a promising treatment strategy for preventing opioid overdose and could
enhance drug treatment when combined with existing modalities. The aim of vaccination is to generate opioid-specific
antibodies (-opioid)s that bind to the drugs and sequester them in the serum, stopping opioids from entering the brain and
other organs, and thus preventing overdose and the sensation sought by the user. While monomeric opioid hapten conjugate
vaccines composed of opioid monomers conjugated to carrier proteins admixed with experimental adjuvants are efficacious
in rodents; the design of current monomeric opioid vaccines is based on monomeric vaccines for cocaine and nicotine that
generated relatively weak, short-lived antibody responses in humans. The goal of this proposal is to develop a polymeric
opioid conjugate vaccine that induces robust, long-lasting -opioid responses in the absence of toxicity. Durable antibody
responses are maintained by long-lived antibody-secreting cells (LLASCs), which are generated upon B cell activation in
the presence of B cell receptor (BCR) crosslinking, recognition of pathogen derived immunostimulatory signals, and
ligation of co-stimulatory signals from helper T cells. To elicit the signals necessary for opioid-specific B cell activation,
our polymeric opioid vaccine against fentanyl—the cause of most opioid overdose deaths—is composed of a water-soluble
copolymer that targets and activates fentanyl-specific B cells, termed p(Fent-co-TLR7), conjugated to the immunogenic
carrier protein tetanus toxin (TT) via a self-immolative linkage that, when cleaved, releases unmodified TT. We will
synthesize p(Fent-co-TLR7) as a random copolymer from a monomer decorated with fentanyl and a second monomer that
activates B cells via toll-like receptor 7 (TLR7). Thus, multivalent TT-p(Fent-co-TLR7) conjugates are designed to target
and crosslink opioid-specific B cell receptors (BCRs), causing B cell activation and BCR-mediated internalization. Once
internalized, TT-p(Fent-co-TLR7) will activate endosomal TLR7, amplifying B cell activation, and release TT. Once
released from p(Fent-co-TLR7) polymers, TT can be efficiently processed and its peptides presented on the surface of B
cells to TT-specific T cells, resulting in optimal T cell activation and the production of signals that drive B cells to
differentiate into LLASCs. In this proposal we will (1) optimize the formulation and demonstrate the mechanisms
responsible for the efficacy of TT-p(Fent-co-TLR7), (2) compare the immunogenicity and durability of the immune
response generated by TT-p(Fent-co-TLR7) to that of monomeric fentanyl-TT conjugate vaccines, and (3) demonstrate the
ability of TT-p(Fent-co-TLR7) to inhibit the behavior effects and lethality of fentanyl. Completion of this proposal will
validate the precl...

## Key facts

- **NIH application ID:** 10287132
- **Project number:** 1R21DA054740-01
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** David Scott Wilson
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $204,688
- **Award type:** 1
- **Project period:** 2021-07-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10287132

## Citation

> US National Institutes of Health, RePORTER application 10287132, The first polymeric opioid conjugate vaccine (1R21DA054740-01). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10287132. Licensed CC0.

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