# Improving the Immune Response to Nanoparticle-Based SARS-CoV-2 Vaccines

> **NIH NIH R21** · UNIVERSITY OF CALIFORNIA-IRVINE · 2023 · $235,500

## Abstract

PROJECT SUMMARY / ABSTRACT
 Vaccines have been very effective at protecting against infectious diseases that pose
serious threats to human health. However, prophylactic vaccines can also be limited, particularly
if antigenic drift occurs to create variants of the pathogen; this can result in vaccines losing
potency over time, needing boosters to confer protection, and lower neutralization efficacy on
emerging viral variants – consequences which are observed in the current COVID-19 pandemic.
Recent studies have shown that the release kinetics of vaccines can be important in establishing
lasting and efficacious immunity. In particular, extending the exposure to antigens can result in
higher antibody titers and increased diversity of neutralizing antibodies that target a more diverse
set of epitopes, relative to immune responses from conventional bolus vaccination. Furthermore,
vaccines made from protein-based nanoparticles can elicit increased antibody production,
broader antigen cross-reactivity, and a more balanced Th1/Th2 response. This study tests the
hypothesis that the synergy in combining the effects of nanoparticle vaccines for effective antigen
presentation, together with a slower release to give a longer exposure to the vaccine, will elicit
increased durability of the immune response and a broader cross-reactivity for emerging viral
variants.
 To test this hypothesis, we propose to encapsulate protein nanoparticle vaccines with a
biodegradable PLGA-PEG-PLGA (PPP)-based polymer to modulate the kinetics of its release
from an in vivo vaccine depot. This extended-release vaccine strategy will then be applied
towards SARS-CoV-2. We will evaluate the durability of the proposed vaccine strategy’s potency
and the breadth of cross-reactive immune responses toward the variants of SARS-CoV-2 and
other types of coronaviruses. Our specific aims are to: (1) create controlled-release nanoparticle
depot vaccines against SARS-CoV-2, and (2) determine the efficacy and immunological
responses to these vaccine nanoparticles that are encapsulated by the polymeric depot. Because
the design of these vaccines is modular and different antigens can be exchanged in a relatively
straightforward approach, the successful implementation of this proposed strategy for coronavirus
antigens could have broader applicability towards the development of vaccines for other infectious
pathogens.

## Key facts

- **NIH application ID:** 10648704
- **Project number:** 1R21AI175980-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA-IRVINE
- **Principal Investigator:** Szu-Wen Wang
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $235,500
- **Award type:** 1
- **Project period:** 2023-09-01 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10648704

## Citation

> US National Institutes of Health, RePORTER application 10648704, Improving the Immune Response to Nanoparticle-Based SARS-CoV-2 Vaccines (1R21AI175980-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10648704. Licensed CC0.

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