Intranasal Flu Vaccine Coadministered with High-Dose Shot More Effective in Older Adults than Shot Alone

A novel investigational intranasal influenza vaccine, when administered along with high-dose inactivated influenza vaccine (IIV) to adults aged 65 years and older resulted in greater immunogenicity compared with administration of high-dose IIV alone, according to findings of a phase 1b study published recently in the journal Lancet Infectious Diseases.¹

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The combination of the nasal and intramuscular vaccines induced seroconversion in nearly half (48%) of participants who received the dual treatment compared with 31% of those who received the shot (Fluzone High-Dose Quadrivalent [Fluzone HD]; Sanofi) plus placebo, according to the study.¹

“Influenza remains a leading cause of seasonal respiratory epidemics, particularly affecting older adults,” Robert Belshe, MD, founder of Saint Louis University’s Center for Vaccine Development, said in a news release from clinical stage vaccine company FluGen, Inc. “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

Between 70% and 85% of annual influenza-related fatalities in the US occur in the vulnerable elderly age group, in many cases despite having received an annual flu shot, the authors wrote. Current injectable influenza vaccines primarily generate serum hemagglutinin antibodies and although approved higher antigen formulations have modest improved efficacy, it appears that serum antibodies alone “do not provide sufficient clinical protection” and particularly in older adults.¹

Intranasal vaccines inhibit viruses from entering the nasal mucosa, the primary site of infection, at all. The investigational supra-seasonal, live, intranasal H3N2 M2-deficient single-replication (M2SR) vaccine has demonstrated the ability to elicit mucosal antibodies and also to protect against drifted strains, according to FluGen.² Investigators hypothesized that combining the impact of both types of vaccines would augment the immune response compared with use of Fluzone HD alone.¹

For the study, the research team enrolled 300 adults aged 65 to 85 years who were considered healthy or who had stable chronic conditions and had not received influenza vaccinations in the past 6 months. Participants were randomly assigned (3:3:3:1)to receive the intranasal 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, both alone and in combination with Fluzone HD and secondary endpoints assessed serum and mucosal antibody levels. Enrollment and randomization took place between June 14 and September 15, 2022.¹

RESULTS

The researchers reported that coadministration of H3N2 M2SR vaccine with Fluzone-HD in the elderly cohort was well tolerated with only 2% to 5% of participants across all groups reporting any treatment-emergent adverse events. They found that intranasal H3N2 M2SR with Fluzone HD induced seroconversion (4-fold or greater increase in hemagglutination inhibition antibodies from baseline to day 29) in 44 (48%) of 91 participants, compared with 28 (31%) of 90 participants who seroconverted in the Fluzone HD plus placebo group (P = .023). H3N2 M2SR with Fluzone HD also induced mucosal and cellular immune responses, according to the study. The authors noted that efficacy will be assessed in additional studies already planned.¹

“The idea of delivering two vaccines in one sitting has become widely accepted,” Paul Radspinner, FluGen president and chief executive officer said in the news release. He invoked an image of an older adult receiving an annual flu shot at a local pharmacy followed by a “quick nasal spray" that would greatly enhance the chances of “not only not becoming seriously ill but of being infected at all. This combination solution could have a tremendous impact on the health of older adults."²

Radspinner also considered the possible impact of concomitant vaccine administration on influenza pandemic protection. “If H5N1 or any other mutating influenza strain were to begin infecting millions of people as SARS-CoV-2 did, imagine the benefits of combining an intranasal vaccine, which could stop most infections from occurring, with a strong antibody-based vaccine shot. The impact on human health could be unequalled in our history.”²

References

1. Eiden J, Fierro C White A. 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. Lancet Infect Dis. Published online July 11, 2024. doi:10.1016/S1473-3099(24)00351-7
2. FluGen's intranasal M2SR flu vaccine, co-administered with high dose vaccine, in older adults shows superiority over flu shot alone. News release. FluGen. July 12, 2024. Accessed July 15, 2024. https://www.globenewswire.com/en/search/organization/FluGen%CE%B4%2520Inc%C2%A7