# Structural vaccinology guided development of a universal CoV vaccine utilizing nucleic acid delivered nanoparticles

> **NIH NIH P01** · WISTAR INSTITUTE · 2022 · $2,626,814

## Abstract

Project Summary
In December 2019 a novel coronavirus, named sudden acute respiratory syndrome coronavirus-2 (SARS-CoV-
2). SARS-CoV-2 rapidly spread around the globe causing a pandemic disease termed coronavirus disease of
2019 (COVID-19). There have been more than 80 million infections and close to two million deaths from COVID-
19 to date. SARS-CoV-2 is the third beta coronavirus of zoonotic origin to cause human epidemics. It is similar
to, but distinct from, Middle East respiratory syndrome coronavirus (MERS-CoV) and sudden acute respiratory
syndrome virus-1 (SARS-CoV-1), both of which have caused outbreaks this century. While several candidate
vaccines for SARS-CoV-2 have recently received emergency use authorization, the longevity of vaccine-induced
responses, the continued emergency of mutation within SARS-CoV-2 strains, and the disproportionate morbidity
and mortality among elderly patient populations present continued challenges to control of SARS-CoV-2. Thus,
vaccine modalities which can address these challenges for SARS-CoV-2 vaccines and allow for targeting of
multiple potentially pandemic coronaviruses simultaneously are greatly needed. Innovative vaccines which
can develop broad immunity against known and newly emergent human coronavirus is a key goal in the
field. The effects of antigen epitope diversity, density, valency, duration of antigen availability, and adjuvant-
induced cytokine environment on the potency and breadth of vaccine-induced Reponses remains unclear.
Nanoparticle vaccine formulations allow the ability to manipulate these variables. We have generated self-
assembling synthetic DNA-launched nanoparticle vaccines (DLNPs) which displayed increased immunogenicity
compared to matched synthetic DNA launched monomer vaccines or protein-in-adjuvant formulations. We
determined that synthetic DNA launched nanoparticles increased both cellular and humoral responses.
Recombinant nanoparticle vaccines are thought to mediate their increased immunogenicity by persisting in the
lymph nodes for extended periods compared to protein antigens, promoting enhanced antigen presentation by
follicular dendritic cells and increasing germinal center formation and humoral immunity. Cell-mediated
responses to nanoparticle vaccines are less well understood but similar mechanisms may be at play. We will
capitalize on the novel in vivo assembling synDLNP platform we have created to manipulate these variables and
determine their effects on acute and long-term responses to CoV antigens in young and aged models.

## Key facts

- **NIH application ID:** 10328138
- **Project number:** 1P01AI165066-01
- **Recipient organization:** WISTAR INSTITUTE
- **Principal Investigator:** Daniel Kulp
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $2,626,814
- **Award type:** 1
- **Project period:** 2022-09-22 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10328138

## Citation

> US National Institutes of Health, RePORTER application 10328138, Structural vaccinology guided development of a universal CoV vaccine utilizing nucleic acid delivered nanoparticles (1P01AI165066-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10328138. Licensed CC0.

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