An intranasal adjuvanted, recombinant influenza A/H5 vaccine primes against diverse H5N1 clades: a phase I trial
Mucosal influenza vaccines offer the potential for improved protection against infection and transmission, but their progress is limited by the lack of defined immune correlates of protection. This study presents a phase I randomized controlled trial of an intranasal recombinant influenza A/H5 vaccine combined with a nanoemulsion adjuvant.
Trial Design and Vaccine Administration
The vaccine was based on hemagglutinin from influenza A/H5 (A/Indonesia/05/2005, clade 2.1) and formulated with the nanoemulsion adjuvant W805EC. Participants received two intranasal doses 28 days apart at three different antigen levels. Control groups received either unadjuvanted H5 or a placebo. Six months later, all participants were boosted with an intramuscular dose of unadjuvanted inactivated A/H5N1 (A/Vietnam/1203/2004, clade 1) vaccine.
Safety Outcomes
- Primary outcomes included solicited and unsolicited adverse events (AEs), laboratory safety abnormalities, medically-attended AEs, immune-mediated conditions, new chronic conditions, and serious adverse events.
- All vaccines were well tolerated with no significant safety concerns reported.
Immune Responses
Following the intranasal vaccination series, hemagglutination inhibition and microneutralization antibody responses were minimal, but the vaccine demonstrated successful mucosal priming and induced broad cross-clade immune responses.
Here, the authors demonstrate "successful mucosal priming and broad cross-clade immune responses, advancing the development of intranasal influenza vaccines."
Summary
This phase I trial supports the safety and mucosal immunogenicity of an intranasal, adjuvanted recombinant influenza A/H5 vaccine, marking progress towards broadly protective mucosal influenza immunization.
Author's summary: This study shows a safe intranasal influenza A/H5 vaccine with nanoemulsion adjuvant that primes mucosal immunity and broad responses across H5N1 clades, advancing vaccine innovation.