# Universal epitopes-based recombinant influenza vaccines

> **NIH NIH R21** · GEORGIA STATE UNIVERSITY · 2020 · $193,854

## Abstract

PROJECT SUMMARY
Current influenza vaccination inducing strain-specific immunity against variable hemagglutinin (HA) proteins is
not effective in providing cross protection against antigenically different epidemic strains and unanticipated new
pandemic viruses. Development of universal vaccines improving cross protection against antigenically different
influenza viruses is a high priority. The fusion peptide (FP) located in the N-terminus of the stalk domain of HA
is universally conserved in both influenza (flu) A and B viruses. Monoclonal and polyclonal antibodies against
FP were shown to exhibit broad neutralizing activity. In preliminary data, we discovered a new HA2 stem
domain near to the FP, which could generate poly IgG antibodies highly cross reactive to different subtype flu
A viruses and both lineage flu B viruses. A neuraminidase (NA) epitope (NA2e) near to the enzymatic active
site was also identified to be universally conserved in all flu A and B viruses. NA2e specific monoclonal
antibody was used to quantitate the NA contents in different flu vaccine lots. NA immunity is considered an
independent protective correlate in addition to HA. Influenza A virus M2 protein extracellular domain (M2e),
which is highly conserved among flu A viruses, has been shown to be a promising target for developing
universal flu A vaccines. However, M2e immunity alone would not provide sufficiently high efficacy of cross
protection.
No vaccines incorporating universally conserved multi epitopes including M2e, FP, stem domains and NA2e
have been developed. Virus-like particle (VLP) platform has been demonstrated to be a promising delivery
vehicle for poor immunogenic but cross protective epitopes. Preliminary data showed that NA2e monoclonal
antibody was able to provide protection after passive inoculation. We hypothesize that new VLP vaccine
constructs inducing antibodies to universal FP-stem domain epitopes and NA2e epitopes in addition to M2e will
enhance the efficacy of cross protection against different strains of flu A and B viruses. In the aim 1, we will
determine whether new recombinant VLP vaccine constructs containing FP-stem, NA2e (or NA), and M2e
epitopes as a standalone vaccine or in combination with HA-based vaccine will enhance the cross protection
against influenza A viruses. In the aim 2, we will determine whether vaccines inducing antibodies to FP-stem
and NA2e epitopes as a standalone vaccine or when supplemented in inactivated virus vaccines will enhance
cross protection against influenza B viruses. This proof-of-concept of two-year project on developing cross
protective vaccines inducing immunity universally conserved new epitopes in both flu A and B viruses would
provide supporting data warranting further advanced preclinical studies.

## Key facts

- **NIH application ID:** 9979495
- **Project number:** 1R21AI147042-01A1
- **Recipient organization:** GEORGIA STATE UNIVERSITY
- **Principal Investigator:** SANG-MOO KANG
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $193,854
- **Award type:** 1
- **Project period:** 2020-02-01 → 2022-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9979495

## Citation

> US National Institutes of Health, RePORTER application 9979495, Universal epitopes-based recombinant influenza vaccines (1R21AI147042-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9979495. Licensed CC0.

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