# Improving Vaccination through Biomimicry: Recapitulating the Antigen Kinetics of Native Infections using a Modular Vaccine Delivery System

> **NIH NIH R21** · RICE UNIVERSITY · 2024 · $187,577

## Abstract

PROJECT SUMMARY/ABSTRACT
Vaccination against infectious disease saves an estimated 4 million lives each year and is one of the most effective and
cost-effective medical advances in human history. Nevertheless, infectious disease remains a leading cause of mortality
worldwide due to (1) the lack of vaccines formulations that confer long-lived immunity and (2) vaccine accessibility
challenges. Adjuvants are capable of enhancing the immune response to antigens; however, there are limits to their
efficacy. For example, alum, the most common clinical adjuvant, is known to enhance humoral immunity but have
relatively little effect on cellular immunity. In addition to exploring new adjuvants, recent studies have begun exploring
the impact of antigen release kinetics on the immune response. Using infusion pumps or sequential injections to
administer antigen over days to weeks, researchers have demonstrated that exponentially increasing antigen release
kinetics over a period of days to weeks can significantly enhance the immune response compared to one bolus injection
despite using the same cumulative antigen dose. These kinetics better mimic a native infection, in which the pathogen
replicates, exposing immune cells to increasing quantities of antigen over time until the infection is cleared, thereby
aligning with the kinetics our immune system has evolved to respond to. Unfortunately, replacing each injection of
soluble antigen currently administered in the clinic with a series of injections spread over days or the continuous use of
an infusion pump for days to weeks is not clinically viable due to cost, invasiveness, and accessibility issues.
In this proposal, we will develop vaccine formulations that exhibit exponential release to mimic the antigen kinetics of
native infections, thereby enhancing vaccine potency without alterations in clinical practice. We have developed a
unique fabrication method, termed Particles Uniformly Liquified and Sealed to Encapsulate Drug (PULSED), that
produces biodegradable microparticles that exhibit pulsatile release after a material-dependent delay. Importantly, this
system is fully modular, so we can combine different particle populations to construct the desired release profile,
overcoming the constraints of other passive vaccine delivery systems whose rates of antigen release inherently
decrease over time. We will first identify microparticle compositions that release diphtheria toxoid (DT) at discrete time
points within two weeks in vitro and in vivo. Next, we will optimize microparticle processing conditions and incorporate
stabilizing excipients to ensure DT is released in its immunity-conferring conformation. Lastly, we will evaluate the
humoral and cellular immune responses to combinations of PULSED particles that, together, exhibit exponential antigen
release and compare those responses to responses elicited by a soluble dose of vaccine as well as microparticle
populations constructed to achieve other antigen ...

## Key facts

- **NIH application ID:** 10953364
- **Project number:** 1R21AI185779-01
- **Recipient organization:** RICE UNIVERSITY
- **Principal Investigator:** Kevin James McHugh
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $187,577
- **Award type:** 1
- **Project period:** 2024-06-12 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10953364

## Citation

> US National Institutes of Health, RePORTER application 10953364, Improving Vaccination through Biomimicry: Recapitulating the Antigen Kinetics of Native Infections using a Modular Vaccine Delivery System (1R21AI185779-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10953364. Licensed CC0.

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