# Engineering immune polyelectrolyte multilayers to study the effect of toll-like receptor agonists on immune response

> **NIH NIH F31** · UNIV OF MARYLAND, COLLEGE PARK · 2020 · $32,162

## Abstract

PROJECT SUMMARY
The initiation of an immune response requires specialized antigen presenting cells to present antigen alongside co-
stimulatory molecules. Activation of toll like receptors (TLRs) is often involved in expression of these co-stimulatory
molecules. TLR pathways detect pathogen-associated molecular patterns (PAMPs), which are common in viruses and
bacteria but not humans. Dozens of TLRs have now been identified in humans and animal models. TLR agonists (TLRas)
have been investigated as vaccine adjuvants due to their ability activate TLRs and upregulate certain co-stimulatory
molecules. Mammalian TLR3, TLR9, TLR13, and TLR7/8 are located within endosomes where they can sense and bind
endocytosed microbial and nucleic acid based PAMPs to drive immune response. Recent studies show activating multiple
TLRs with their respective TLR agonists (TLRas) increases the efficacy of vaccines for infectious diseases and cancer.
Therefore delivering programmable combinations of TLRas with disease relevant antigen may be exploited to create a
strong antigen-specific immune responses tuned for particular pathogens. While traditional co-delivery methods often rely
on biomaterials, biomaterials themselves often elicit immune responses that can confound vaccine design because the carrier
changes the response to the other vaccines components (e.g., antigen, TLRa). Our lab has previously developed immune
polyelectrolyte multilayers (iPEMs), a modular platform exploiting electrostatic interactions to create carrier-free capsules
composed entirely of antigen and single TLRa. This strategy allows co-delivery of tunable signals without extraneous
components, providing a means to isolate the impact of specific TLRas in polarizing immunity. This proposal will use the
iPEM platform to reveal how co-delivering different combinations and relative ratios of TLRas changes the magnitude and
type of the resulting immune response during generation of antigen-specific immunity. In preliminary experiments I have
shown iPEMs deliver TLRa cargo to endosomes resulting in time-dependent immune activation in vitro. Our lab has further
shown that iPEMs composed of a model antigen and a single TLRa enhance antigen-specific immune response compared
to soluble delivery of the same components. Additionally, iPEMs can be synthesized from defined combinations and ratios
of different classes of TLRas. This proposal will build on these data to 1) Elucidate the effect of iPEM composition
(combinations of TLRas) on the in vitro trafficking and immune function, 2) Test if iPEM composition can be used to
program TLR signaling in vivo, and 3) Confirm that activating multiple TLRas using iPEMs improves immune response
and survival during a mouse model of melanoma. This model will be used as a functional test bed since recent studies
revealed that treatment with two TLRas increased survival in a mouse model of melanoma. The knowledge gained from
this proposal will show how co-delivery of dif...

## Key facts

- **NIH application ID:** 9812183
- **Project number:** 5F31EB027579-02
- **Recipient organization:** UNIV OF MARYLAND, COLLEGE PARK
- **Principal Investigator:** Michelle Lynn Bookstaver
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $32,162
- **Award type:** 5
- **Project period:** 2018-12-01 → 2020-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9812183

## Citation

> US National Institutes of Health, RePORTER application 9812183, Engineering immune polyelectrolyte multilayers to study the effect of toll-like receptor agonists on immune response (5F31EB027579-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9812183. Licensed CC0.

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