# A Totally Synthetic Immunostimulator that Targets Toll-like Receptor 2 and NOD2: Toward Improved Influenza Vaccines

> **NIH ALLCDC R43** · TEICHOS LABORATORIES, LLC · 2021 · $243,000

## Abstract

Influenza viruses cause seasonal epidemics and occasional pandemics that inflict significant global morbidity and
mortality. The threat of emerging influenza infections has stimulated development of vaccines to induce broadly
protective and durable immunity. Technology that may boost immunogenicity safely beyond levels afforded by
currently used adjuvants is critical to advancing vaccine design and development. While research over several
decades has identified broad peptidoglycan (PGN) immunostimulatory properties with potential application as an
adjuvant, technical, regulatory, and development challenges have prevented development of native PGN for
vaccine applications. Teichos Laboratories, LLC (Teichos) proprietary technology produces a platform of
macromolecular immunostimulatory biologics by chemoenzymatic total synthesis of authentic PGN core structure,
termed sPGN. Preliminary results with a prototype sPGN, TL-001, support its utility as a vaccine adjuvant. TL-001
is a single-strand, uncrosslinked, macromolecular (ca. 20 – 200 kDa) sPGN produced by robust, scalable, and
flexible total synthesis from commercially available small molecules, standard reagents, and a single enzyme.
Therefore, TL-001, like all sPGN, is produced free of the adventitious, and often potent, contaminant immune reactive
materials that accompany similar macromolecules isolated from microorganisms. In a laboratory vaccination
model, low dose TL-001 induces a robust response that is mediated through TLR2 and NOD2 receptors to stimulate
coordinated innate and adaptive immune responses through two synergistic layers of signalling that amplify
antibody production and T cell activation. Neither toxicity nor reactogenicity were observed when high dose sPGN
was administered to laboratory animals. This proposal seeks support to advance TL-001 from discovery
(preliminary data) to development phase (application to disease prevention studies) by conducting proof-of-
principle experiments to validate development as a human influenza vaccine adjuvant. We will produce a test lot of
TL-001 that will be evaluated to define the role of TLR2 and other cellular mechanisms in mediating the
immunostimulatory responses in human monocytes and macrophages. We will characterize the antibody and T
cell responses to TL-001 using an influenza H1 subunit vaccination model in mice. Anticipated technical success
in the proposed studies will help support Phase II assessments of TL-001 safety, protection in lethal influenza
challenge models, alternate routes of administration, and formulation development.

## Key facts

- **NIH application ID:** 10254747
- **Project number:** 1R43IP001167-01
- **Recipient organization:** TEICHOS LABORATORIES, LLC
- **Principal Investigator:** Larry C. Blaszczak
- **Activity code:** R43 (R01, R21, SBIR, etc.)
- **Funding institute:** ALLCDC
- **Fiscal year:** 2021
- **Award amount:** $243,000
- **Award type:** 1
- **Project period:** 2021-09-30 → 2022-09-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10254747

## Citation

> US National Institutes of Health, RePORTER application 10254747, A Totally Synthetic Immunostimulator that Targets Toll-like Receptor 2 and NOD2: Toward Improved Influenza Vaccines (1R43IP001167-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10254747. Licensed CC0.

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