AI Article Synopsis
- A phase 1b study evaluated the safety and immune response of an intranasal M2-deficient single replication (M2SR) influenza vaccine in adults aged 18-49.
- Subjects received two doses of the vaccine, with results showing significant increases in neutralizing antibodies after higher doses; 80.6% demonstrated a response after the 109 TCID50 dose.
- The vaccine was well tolerated and elicited both mucosal and cellular immune responses, suggesting its potential effectiveness against drifted H3N2 influenza strains.
Article Abstract
Background: We previously demonstrated that an intranasal dose of 108 50% tissue culture infectious dose (TCID50) M2-deficient single replication (M2SR) influenza vaccine protected against highly drifted H3N2 influenza challenge in a subset of subjects who demonstrated ≥2-fold increase in microneutralization (MN) antibodies to Belgium2015 (the challenge strain) after vaccination. Here, we describe a phase 1b, observer-blinded, dose-escalation study demonstrating an increased proportion of responders with this signal of immune protection.
Methods: Serosusceptible subjects aged 18-49 years were randomized to receive 2 doses (108-109 TCID50) of M2SR or placebo administered 28 days apart. Clinical specimens were collected before and after each dose. The primary objective was to demonstrate safety of M2SR vaccines.
Results: The vaccine was well tolerated at all dose levels. Against Belgium2015, ≥ 2-fold increases in MN antibodies were noted among 40% (95% confidence interval [CI], 24.9%-56.7%) of subjects following a single 108 TCID50 M2SR dose and among 80.6% (95% CI, 61.4%-92.3%) after 109 dose (P < .001). A single 109 TCID50 dose of M2SR generated ≥4-fold hemagglutination inhibition antibody seroconversion against the vaccine strain in 71% (95% CI, 52.0%-85.8%) of recipients. Mucosal and cellular immune responses were also induced.
Conclusions: These results indicate that M2SR may provide substantial protection against infection with highly drifted strains of H3N2 influenza.
Clinical Trials Registration: NCT03999554.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9796169 | PMC |
| http://dx.doi.org/10.1093/infdis/jiac433 | DOI Listing |
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