# Influenza vaccines inducing broadly cross protective immunity

> **NIH NIH R01** · GEORGIA STATE UNIVERSITY · 2020 · $501,250

## Abstract

Project summary:
Current platforms of inactivated split virus (split) and live attenuated influenza virus (LAIV) vaccines
based on immunity to the hemagglutinin (HA) hypervariable protein do not provide effective cross
protection against antigenically distinct new strains. Developing a novel vaccine that improves the
efficacy and breadth of cross protection is therefore of high priority. Previous studies aimed to
generate universal influenza vaccines suggest that universal antigenic targets are insufficient to serve
as a standalone vaccine due to low efficacy of protection compared to HA-matched split vaccine
despite the benefits of broadening cross protection. Because of this limitation, universal influenza
vaccine candidates are not expected to replace current influenza vaccine platforms.
Our progress report demonstrated that a combination of commercial HA-based influenza split and M2
ectodomain (M2e) vaccines significantly improved the efficacy of cross protection compared to either
M2e- or HA-based vaccine alone. Enhanced cross protection by M2e-supplemented HA vaccination
was consistently observed in studies using mouse and ferret animal models. In this renewal
application, we propose groundbreaking approaches to increase the intrinsic capacity of current
influenza vaccine platforms (LAIV, Split) to confer cross protection by incorporating
conserved M2e epitopes into HA in a chimeric form. In our preliminary studies, we rescued
recombinant influenza viruses expressing a chimeric HA molecule with conserved M2e epitopes
(4xM2e-HA, M2e-HA) using reverse genetics. More importantly, these recombinant influenza virus
vaccines with chimeric HA containing M2e epitopes could confer significantly enhanced protection
against a broader range of viruses (H1, H3, and H5 subtypes) by inducing cross protective M2e
antibodies without compromising HA immunity. In aim 1, we will test the hypothesis that
recombinant seasonal (H1N1 and H3N2) LAIV and inactivated split vaccines with chimeric HA
containing M2e epitopes will enhance the efficacy of cross protection by inducing immunity to both
M2e and HA. Replication competent recombinant seasonal H1N1 and H3N2 influenza viruses will be
constructed by engineering chimeric M2e-HA molecules. Aim 2 will investigate the contribution of
cellular and humoral immune mechanisms to cross protection by recombinant influenza virus vaccines
using wild type and mutant mouse models. Aim 3 will validate the efficacy of cross protection by
recombinant influenza virus vaccines in ferrets, the most relevant small-animal model for the
assessment of influenza vaccines.

## Key facts

- **NIH application ID:** 9932879
- **Project number:** 5R01AI093772-10
- **Recipient organization:** GEORGIA STATE UNIVERSITY
- **Principal Investigator:** SANG-MOO KANG
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $501,250
- **Award type:** 5
- **Project period:** 2011-05-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9932879

## Citation

> US National Institutes of Health, RePORTER application 9932879, Influenza vaccines inducing broadly cross protective immunity (5R01AI093772-10). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9932879. Licensed CC0.

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