# Multivalent nanocluster universal influenza vaccine given by microneedle patch

> **NIH NIH R01** · GEORGIA STATE UNIVERSITY · 2020 · $764,738

## Abstract

SUMMARY Influenza is a major public health risk. Current seasonal influenza vaccines are effective in
protecting against closely matched viruses in healthy adults. Because continuous genetic changes occur in
influenza, there are major limitations to seasonal influenza vaccines including the need to produce new vaccines
every season, uncertainty in selecting vaccin strains, and the inability to prevent novel influenza pandemics. A
universal influenza vaccine will overcome these challenges. In our previous and preliminary studies, we have
produced double-layered protein nanoclusters by desolvating the conserved ectodomain of the influenza M2
protein (M2e) into nanoparticles as cores and crosslinking influenza A trimeric hemagglutinin (HA) stalk antigens
onto the core surfaces. We have also desolvated influenza internal nucleoprotein (NP) into particulate cores and
cross linked M2e to generate double-layered nanoclusters. The resulting layered nanoclusters induced cross
protection against viruses from both phylogenetic groups of influenza A, including pandemic potential avian
strains.
Both influenza A and B can cause epidemics. In this proposal, we will develop a multivalent double-layered
nanocluster universal influenza vaccine composed of newly designed, conserved, antigenic proteins from both
influenza A and B, and a molecular adjuvant. This nanocluster vaccine will induce strong cross immune
protection against both influenza A and B in different laboratory animal models. The optimal nanocluster
formulation will be encapsulated into dissolvable microneedle (MN) patches to develop a syringe-free, painless,
thermostable, and self-administered skin-given universal influenza vaccine. The three specific aims are:
Aim 1. Generate constructs of trimeric HA stalk antigen from influenza B and conserved NPs from both
influenza A and B, fabricate and characterize nanoclusters from these and previously designed
conserved antigenic proteins. We have generated structure-stabilized HA stalk proteins from both
phylogenetic groups of influenza A (hrH1 and hrH3) and tetrameric M2e. We will fabricate novel double-layered
nanoclusters from previous and new designed conserved influenza antigenic proteins.
Aim 2. Test whether the layered nanoclusters or a multivalent optimal combination will induce protection
against viruses spanning both influenza A and influenza B in mice. We will optimize a vaccine formulation
inducing broadly reactive immune responses and cross protection in mice and further studies in Aim 3.
Aim 3. Encapsulate the optimal multivalent nanocluster formulation into dissolvable MN patches and
test the breadth of protection of the MN-based skin vaccination in both mice and ferrets. Dissolvable MN
patch-based skin influenza vaccination has many advantages over conventional syringe injection including
painless, needle-free, self-administration and cold chain-independent distribution.
Overall, our research will develop a broadly cross-protective universa...

## Key facts

- **NIH application ID:** 9870852
- **Project number:** 5R01AI143844-02
- **Recipient organization:** GEORGIA STATE UNIVERSITY
- **Principal Investigator:** Baozhong Wang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $764,738
- **Award type:** 5
- **Project period:** 2019-02-12 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9870852

## Citation

> US National Institutes of Health, RePORTER application 9870852, Multivalent nanocluster universal influenza vaccine given by microneedle patch (5R01AI143844-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9870852. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*