FluGen, Inc is a clinical-stage vaccine company focused on improving vaccine efficacy for respiratory diseases, with its lead candidate being M2SR, a novel intranasal flu vaccine.

Image credits: FluGen

A recent study published in The Lancet assessed the safety, tolerability, and immunological response to FluGen Inc’s investigational supra-seasonal, live, single-replication intranasal influenza vaccine (M2SR) when administered with Sanofi’s Fluzone High-Dose (HD) inactivated influenza vaccine (IIV). Current inactivated influenza vaccines primarily generate serum antibodies, leading to low vaccine effectiveness in older adults 65-85. The coadministration of the H3N2 M2SR vaccine with Fluzone HD demonstrated enhanced immunogenicity compared to Fluzone HD alone.

“Influenza remains a leading cause of seasonal respiratory epidemics, particularly affecting older adults,” stated Robert Belshe, MD, founder of Saint Louis University’s Center for Vaccine Development. “Current vaccines are limited in duration, efficacy against mutated strains, and prevention of initial infection in the upper respiratory tract. The results from this study may offer a solution that could significantly reduce illness in older adults.”²

This multicenter, randomized, double-blind, phase 1b trial included healthy individuals aged 65–85 years and those with stable chronic conditions who had not received influenza vaccinations in the past six months. Participants were assigned to receive either the H3N2 M2SR vaccine with Fluzone HD, H3N2 M2SR with placebo, Fluzone HD with placebo, or placebo alone. The primary outcome assessed the safety of H3N2 M2SR, while secondary endpoints included serum and mucosal antibody levels.¹

“The concept of administering two vaccines in a single visit has gained widespread acceptance,” noted Paul Radspinner, President and CEO of FluGen. “Imagine receiving your flu shot and a quick nasal spray simultaneously, significantly enhancing your protection against severe illness and infection. This dual approach could profoundly impact the health of older adults.”²

Immunogenicity results indicated that M2SR with Fluzone HD induced seroconversion in 44 of 91 participants, compared to 28 of 90 in the Fluzone HD plus placebo group. Additionally, M2SR with Fluzone HD induced significant mucosal and cellular immune responses.¹

Radspinner also highlighted the potential for pandemic preparedness, “If a virulent strain like H5N1 were to emerge, the combination of an intranasal vaccine, which could prevent most infections, with a robust antibody-based vaccine could revolutionize public health outcomes.”²

Intranasal vaccines are designed to provide localized immune defense at the site of infection, helping to prevent influenza viruses from entering the nasal mucosa. The intranasal M2SR vaccine has demonstrated the ability to elicit mucosal antibodies and provide protection against drifted strains while maintaining durability. In contrast, traditional flu shots primarily generate systemic antibodies after viral entry into the body. The combination of these two approaches offers comprehensive protection.²

FluGen’s June 2022 Kickoff

Between June 14 and September 15, 2022, a trial enrolled 305 participants who were randomly assigned to receive one of four treatments: the H3N2 M2SR vaccine plus placebo, H3N2 M2SR plus Fluzone HD, Fluzone HD plus placebo, or placebo alone. The safety analysis included all participants. Common local side effects reported within eight days included runny nose (43% in the M2SR plus placebo group, 38% in the M2SR plus Fluzone HD group) and nasal congestion (51% and 35%, respectively). Systemic side effects included sore throat (28%) and reduced activity (26%) in the M2SR plus Fluzone HD group. Adverse events were low across all groups, with one serious event reported in the Fluzone HD plus placebo group.¹

FluGen announced that it had begun dosing its first subject in a groundbreaking study targeting older adults aged 65-85 years,³

“This study is the first of its kind to combine intranasal vaccine delivery with intramuscular shots to assess the potential for boosting efficacy and reducing transmission,” stated Yoshihiro Kawaoka, Professor of Virology at the University of Wisconsin and FluGen co-founder.³

Overall, M2SR stimulates a broad immune response has shown long-lasting protection against various influenza strains, and has potential as a vaccine vector for other diseases, including a COVID-19/flu combination and RSV. These results underscore M2SR’s potential as an effective influenza vaccination strategy, particularly for older adults at higher risk. Further efficacy studies are planned.

References

1. Eiden J, Fierro C, White A, et. al. Safety and immunogenicity of the intranasal H3N2 M2-deficient single-replication influenza vaccine alone or coadministered with an inactivated influenza vaccine (Fluzone High-Dose Quadrivalent) in adults aged 65–85 years in the USA: a multicentre, randomised, double-blind, double-dummy, phase 1b trial. TheLancet. Published July 11, 2024. Accessed July 12, 2024. Doi: https://doi.org/10.1016/S1473-3099(24)00351-7

2. FluGen. FluGen’s Intranasal M2SR Flu Vaccine, Co-Administered with High Dose Vaccine, in Older Adults Shows Superiority Over Flu Shot Alone. GlobalNewswire. Published July 12, 2024. Accessed July 12, 2024. https://www.globenewswire.com/news-release/2024/07/12/2912327/0/en/FluGen-s-Intranasal-M2SR-Flu-Vaccine-Co-Administered-with-High-Dose-Vaccine-in-Older-Adults-Shows-Superiority-Over-Flu-Shot-Alone.html

3. FluGen. FluGen Announces First Subject Dosed in Phase 1b Clinical Trial of its Intranasal M2SR Flu Vaccine, Co-Administered with High Dose Vaccine, in Older Adults. PRNewswire. Published June 22, 2022. Accessed July 12, 2024. https://www.prnewswire.com/news-releases/flugen-announces-first-subject-dosed-in-phase-1b-clinical-trial-of-its-intranasal-m2sr-flu-vaccine-co-administered-with-high-dose-vaccine-in-older-adults-301572735.html