# Lipid nanoparticles as novel adjuvants inducing effective T follicular helper cell and humoral immune responses

> **NIH NIH R01** · UNIVERSITY OF PENNSYLVANIA · 2020 · $622,103

## Abstract

ABSTRACT
Vaccines prevent hundreds of millions of illnesses and save millions of lives every year. Various types of
licensed vaccines (live attenuated and inactivated pathogens, adjuvanted protein subunits) provide some level
of protection against a variety of dangerous illnesses. However, there are multiple pathogens for which no
effective vaccines are available. Protective immunity against many pathogens can be achieved through long-
lived and high-affinity antibody responses, which are driven by T follicular helper (Tfh) cells. Tfh cells are
required for the formation and maintenance of germinal centers (GC), where B cell affinity maturation, class
switch, and development of long-lived plasma and memory B cells occur. Thus, the magnitude or quality of
antibody responses induced by a vaccine is shaped by its ability to induce Tfh cells. The identification of
vaccine platforms or adjuvants that induce potent Tfh cell responses and broadly protective and durable
antibody responses is a critical need in vaccinology. We have identified a potent vaccine adjuvant, lipid
nanoparticles (LNPs), which induce strong Tfh cell differentiation and durable antibody responses after a single
immunization when combined with protein subunits, inactivated virus or antigen-encoding mRNA. Importantly,
our preliminary studies demonstrated the superiority of LNP's adjuvant activity over the FDA-approved vaccine
adjuvant, MF59, in comparative studies. This proposal will aim to extend our preliminary findings, examine
LNP's adjuvanticity in non-human primate immunization studies and investigate the mechanisms of action of
LNPs. In 3 specific aims we will: 1.) Determine LNP's adjuvanticity in multiple vaccine platforms in mice. 2.)
Assess the potency of LNP-adjuvanted Zika vaccines in non-human primates. 3.) Uncover LNP-induced
immune mechanisms that regulate the biology of Tfh cells.
This proposal aims to demonstrate that LNPs can be used as adjuvants in various conventional (inactivated
pathogen and protein subunits) and unconventional (mRNA, DNA) vaccine types to induce strong Tfh cell and
durable neutralizing antibody responses. This finding could have a significant impact on vaccine development
as no licensed vaccines or adjuvants have been shown to potently activate Tfh cells that are critical for durable
protective antibody responses against many pathogens. We believe that the data generated in this proposal
will be capable of moving this vaccine adjuvant towards clinical trials.

## Key facts

- **NIH application ID:** 10028088
- **Project number:** 1R01AI153064-01
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Norbert Pardi
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $622,103
- **Award type:** 1
- **Project period:** 2020-09-01 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10028088

## Citation

> US National Institutes of Health, RePORTER application 10028088, Lipid nanoparticles as novel adjuvants inducing effective T follicular helper cell and humoral immune responses (1R01AI153064-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10028088. Licensed CC0.

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