# Biomimetic nanoparticles to enhance the breadth of influenza vaccines

> **NIH NIH R01** · MASSACHUSETTS GENERAL HOSPITAL · 2020 · $445,294

## Abstract

Abstract
Current influenza (flu) vaccines are effective only for closely matched flu viral strains and must be updated
annually to address constant antigenic shift/drifts of surface hemagglutinin (HA) and/or neuraminidase (NA) of
the virus. Even with annual update, there have been years in which flu vaccines were ineffective due to
significant differences in antigenicity of HA and/or NA between the strains used for preparing the vaccines and
the circulating ones, leaving us at high risk of pandemics in case a new and highly pathological virus emerges.
It is without any doubt that a “Universal” flu vaccine that can protect against both seasonal (matched or
mismatched) and pandemic flu viruses is urgently needed, but it remains “an alchemist’s dream” so far. We
developed a novel adjuvant by encapsulation of cGAMP, an agonist of the stimulator of interferon (IFN) gene
(STING), into pulmonary surfactant (PS)-biomimetic liposomes (PS-GMNP). The adjuvant, alongside an
inactivated flu vaccine, robustly stimulated humoral and CD8+ T cell immune responses that resemble those
ocurring during the early phase of viral infection both in magnitude and in dynamics. Strikingly, a single dose of
PS-GMNP-adjuvant flu vaccine elicited strong cross-protection against a lethal challenge of diverse
heterosubtypic flu A viruses as early as 2 days after immunization. While stimulating robust heterosubtypic
immunity, the adjuvant did not cause any adverse events in lung histology, body weight or temperature, in
sharp contrast to the severe lung inflammation and death caused by flu viral infection. In this proposal, we will
investigate the cellular and humoral immune responses essential to the cross-protection induced by PS-
GMNP-adjuvanted flu vaccines. Specifically, we will determine whether PS-GMNP can expand cross-reactive
CD8+ T cells and induce broadly neutralizing antibodies (bnAbs), pivotal to PS-GMNP-induced cross-
protection. In Aim 2, we will preclude any adverse effects of pre-existing immunity on the adjuvanticity of PS-
GMNP and extend the cross-protection to pre-pandemic wild type H5N1 and H7N9 viruses to establish its
clinical potentials. Distinguished from conventional adjuvants that activate primarily antigen-presenting cells
(APCs), cGAMP delivered by PS-GMNP activated both alveolar macrophages (aMɸ) and alveolar epithelial
cells (AEC), which can be crucial since similar activation of these two types of cells is also observed during flu
viral infection. Two alternative approaches will be employed in Aim 3 to corroborate indispensable function of
AEC and/or aMɸ in PS-GMNP-mediated heterosubtypic immunity, including a blockade of cell-gap junctions
and generation of chimeric mice of wild type and STING-deficient bone marrow (BM) cells. The study, if
successful, could provide invaluable information about clinical potentials for PS-GMNP to widen the breadth of
existing flu vaccines toward a “Universe” one, which will have a huge and immediate impact on glob...

## Key facts

- **NIH application ID:** 9971856
- **Project number:** 1R01AI146588-01A1
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Mei X Wu
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $445,294
- **Award type:** 1
- **Project period:** 2020-08-07 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9971856

## Citation

> US National Institutes of Health, RePORTER application 9971856, Biomimetic nanoparticles to enhance the breadth of influenza vaccines (1R01AI146588-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9971856. Licensed CC0.

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