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 but currently lack clear immune correlates of protection. This study reports a phase I randomized, controlled trial evaluating an intranasal recombinant influenza A/H5 vaccine combined with a nanoemulsion adjuvant (W805EC).
Study Design and Methods
The vaccine, based on hemagglutinin from A/Indonesia/05/2005 (clade 2.1), was given intranasally in two doses spaced 28 days apart at three antigen levels. Control groups received either unadjuvanted H5 or placebo. Six months later, all participants received an intramuscular booster with an unadjuvanted inactivated A/H5N1 vaccine derived from A/Vietnam/1203/2004 (clade 1).
Safety Outcomes
- Primary outcomes included solicited and unsolicited adverse events (AEs), laboratory safety measures, medically-attended AEs, potential immune-mediated conditions, new chronic conditions, and serious AEs.
- All vaccines were well tolerated without significant safety concerns.
Immune Responses
Following the intranasal doses, hemagglutination inhibition and microneutralization antibody responses were notably low. However, the vaccine demonstrated effective mucosal priming and broad cross-clade immune activation upon boosting.
"Mucosal influenza vaccines may provide improved protection against infection and transmission, but their development is hindered by absence of immune correlates of protection."
"After the intranasal series, hemagglutination inhibition and microneutralization responses are minimal."
Conclusion
This trial advances the development of intranasal influenza vaccines by demonstrating safety and mucosal immune priming, which supports further evaluation for broad protective effects against diverse H5N1 clades.
Author's summary: The study shows that an intranasal recombinant influenza A/H5 vaccine with nanoemulsion adjuvant is safe and primes mucosal immunity, enabling broad responses after boosting with an inactivated vaccine.