The Future of Influenza Vaccination: Insights from FluGen’s M2SR Vaccine Study
Paul Radspinner, MBA, president and CEO of FluGen, addresses the safety profile, noting the low adverse event rates highlighting the safety and tolerability of the H3N2 M2SR influenza vaccine.
Paul Radspinner, MBA, president and CEO of FluGen
A recent study published in The Lancet assessed the safety, tolerability, and immunological response to FluGen’s investigational supra-seasonal, live, single-replication intranasal influenza vaccine (M2SR) when administered alongside Sanofi’s Fluzone High-Dose (HD) inactivated influenza vaccine (IIV). Current inactivated influenza vaccines primarily generate serum antibodies, which leads to lower effectiveness in older adults aged 65-85. The coadministration of the H3N2 M2SR vaccine with Fluzone High-Dose was well tolerated and demonstrated enhanced immunogenicity compared with Fluzone HD alone, suggesting improved efficacy for older adults.1
Contagion® secured an exclusive interview with Paul Radspinner, MBA, president and CEO of FluGen Inc, to learn more about these data. Radspinner discusses the efficacy and safety of the H3N2 M2SR influenza vaccine, highlighting its enhanced immune responses when coadministered with Sanofi’s Fluzone HD vaccine in older adults, along with plans for further research and regulatory approval to improve vaccination strategies for at-risk populations.
Contagion: What specific immune responses did you observe with the H3N2 M2SR vaccine compared to Fluzone HD alone, and how do these responses correlate with potential protection against influenza?
Radspinner: We evaluated mucosal secretory IgA Cam2020 hemagglutinin ELISA titers, serum HAI antibody titers, and cell-mediated immune responses after vaccination. This was done for all 4 cohorts. The results were as follows:
- Mucosal secretory IgA- M2SR alone and when coadministered with Fluzone High Dose (HD) generated statistically significantly higher increases in GMT and GMFR after vaccination than either Fluzone HD alone or placebo. This was true for serosusceptible subjects as well. In addition, both M2SR and the two vaccines coadministered generated statistically significantly higher increases in seroprotected subjects when compared to Fluzone HD alone
- Serum HAI antibody titers- M2SR coadministered with Fluzone HD generated statistically significantly higher HAI titer increases at the ≥2-fold and ≥4-fold levels vs either Fluzone HD, M2SR, or placebo alone. In addition, the coadministration of the two vaccines delivered statistically significantly higher GMTs and GMFRs vs the other 3 cohorts.
- Cell-mediated immune responses- M2SR and the coadministration of M2SR and Fluzone HD generated statistically significantly higher increases in the percentage of subjects with ≥2-fold rises in IFNγ-producing cells, granzyme B-producing cells and dual IFNγ and granzyme B-producing cells.
Of these 3 immunological areas, only serum HAI is an established correlate of protection by regulatory agencies around the world. Fluzone HD has already established itself with HAI correlates and in head-to-head efficacy studies vs standard IIV as superior. This study suggests that the statistically significant increases in HAI seroconversion may lead to superior protection in older adults based on HAI alone. In addition, the results from the mucosal and cellular assays showing the percentage of subjects with ≥2-fold rises also suggest the potential for increased efficacy vs. either vaccine alone. In a challenge study we conducted with a 7-year drifted virus, FluGen was able to show a correlation between ≥2-fold increases and protection from infection and illness. Ultimately head-to-head efficacy studies will determine whether these immunological increases correlate with superior protection.
From June 14 to September 15, 2022, 305 participants were randomly assigned to receive either the H3N2 M2SR vaccine with placebo (n=89), H3N2 M2SR with Fluzone HD (n = 94), Fluzone HD with placebo (n = 92), or placebo alone (n = 30). All were included in the safety analysis. In the M2SR groups, common local symptoms within 8 days included rhinorrhea (43% and 38%) and nasal congestion (51% and 35%). Injection-site pain was reported by 8% and 49%, respectively. Common systemic symptoms were sore throat (28%) for M2SR and decreased activity (26%) for M2SR plus Fluzone HD. In the Fluzone HD plus placebo group, injection-site pain (48%) and muscle aches (22%) were most frequent.2
Can you elaborate on the safety profile of the H3N2 M2SR vaccine, particularly regarding any adverse events that were observed during the trial?
M2SR has been studied in over 700 subjects and is generally safe and well-tolerated. We have seen no drug-related SAEs in any of our studies and the most common side effects have been mild nasal congestion or rhinorrhoea. In this study, 10% of the M2SR cohort and 15% of the M2SR/Fluzone HD group showed at least one Treatment-Emergent Adverse Event (TEAE) while Fluzone HD and placebo showed 17% and 20% respectively. There was only one SAE in this study, which was in the Fluzone HD cohort.
What are the next steps in your research, and how do you plan to evaluate the long-term efficacy of the H3N2 M2SR vaccine in older adults?
Two paths could be pursued to secure approval of the coadministration of M2SR with Fluzone HD or another IIV. First, would be to pursue the standard Accelerated Approval path which allows approval based on HAI serological responses in vaccinated subjects. This of course would first have to be agreed to by the FDA. If approved via this path, a full efficacy study would be conducted thereafter measuring M2SR and Fluzone HD vs Fluzone HD alone. The second path is to establish M2SR's superior efficacy alone vs IIV. The first step would be to conduct a challenge study as proof of concept and then a larger efficacy study for approval. We are currently pursuing both paths.
Overall, M2SR elicits a broad immune response and has demonstrated long-lasting protection against multiple influenza strains. It also shows promise as a vaccine vector for other diseases, including a COVID-19/flu combination and RSV. These findings highlight M2SR's potential as an effective influenza vaccination strategy, especially for older adults at greater risk. Additional efficacy studies are planned.
