# Genetically detoxified tetanus toxin for use in vaccines

> **NIH NIH R43** · FINA BIOSOLUTIONS, LLC · 2020 · $289,089

## Abstract

Summary
Tetanus and diphtheria toxoids are highly effective vaccines for preventing diseases. As “carrier proteins”,
tetanus and diphtheria toxoids enhance the immunogenicity of small molecules and polysaccharides. However,
tetanus toxoid (TTxd) represents only 20-70% of the protein in the TTxd vaccine and the TTxd vaccine
contains hundreds of ‘un-intended/contaminant’ clostridial proteins. Purification is often needed prior to TTxd
use a conjugate vaccine carrier. TT is detoxified with formaldehyde, using an over 30-day incubation that
blocks a subset lysines that cannot then be used for conjugation with antigens. Collaborators at the Medical
College of Wisconsin have engineered a full-length, atoxic tetanus toxin (M8TT) with 8 independent mutations
reducing catalysis, translocation, and binding functions. Here, Fina Biosolutions (FinaBio) proposes to develop
and manufacture M8TT in a proprietary engineered E. coli strain that has a unique oxidative environment. This
strain has been used successfully to produce multi-grams/L amounts of CRM197, a mutated form of diphtheria
toxin that has been successfully used as a recombinantly expressed vaccine protein carrier. This proposal
uses recombinant DNA technology, biotechnology, biochemistry and immunological approaches to produce
and test the immunological potency of this next generation conjugate tetanus vaccine platform.
The Specific Aims for Phase I are to: subclone and scale up production and purify > 1 g/L of M8TT at >95%
purity; and to test the immunological properties of M8TT versus conventional TTxd to produce a conjugate of
Hemophilus influenzae subtype b polyribitol phosphate sugar PRP conjugated to M8TT and TTxd to determine
if PRP-TTxd is a more potent conjugate vaccine to PRP and TT than PRP-TTxd. If successful, Phase II
studies will optimize the M8TT manufacturing process to 50 L production scale and characterize the product for
safety and efficacy in pre-clinical trials. In addition, the utility of M8TT as a vaccine carrier protein will be further
explored with additional antigens, including small molecules and other polysaccharides. Ultimately, a superior
tetanus vaccine protein will be commercialized by advancing a 50-year old industrial technology with a new,
modernized, economic, effective, and safe conjugate TT vaccine platform.

## Key facts

- **NIH application ID:** 10006309
- **Project number:** 1R43AI148018-01A1
- **Recipient organization:** FINA BIOSOLUTIONS, LLC
- **Principal Investigator:** Andrew Lees
- **Activity code:** R43 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $289,089
- **Award type:** 1
- **Project period:** 2020-04-20 → 2021-09-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10006309

## Citation

> US National Institutes of Health, RePORTER application 10006309, Genetically detoxified tetanus toxin for use in vaccines (1R43AI148018-01A1). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/10006309. Licensed CC0.

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