The avian influenza vaccine Emerflu. Why did it fail?

Abstract

Emerflu is an inactivated, split-virion pandemic preparedness vaccine, containing 30 μg of hemagglutinin (HA) and 600 μg of aluminum hydroxide adjuvant. It is administered in two doses, 3 weeks apart. Only moderate immunogenicity was evident from clinical studies with the vaccine in adults, and HA antibody responses were below the criteria established by the EMA and US FDA for licensure. With the exception of Australia, the vaccine remains unlicensed. Further clinical development appears to have been suspended, and newer adjuvants such as MF59 and AS03 have since demonstrated safety and superior immunogenicity with lower HA doses. Emerflu is symbolic of the failure of aluminum salts as an adjuvant for influenza vaccines. Reasons for this failure are unclear, and may reflect problems with the adjuvant-antigen complex or interference in the immune response by heterosubtypic immunity.

Keywords:

• adjuvant
• alum
• avian
• Emerflu
• H5N1
• influenza
• split
• vaccine
• virion

Financial & competing interests disclosure

BE Young is site principal investigator for a Sanofi sponsored vaccine trial. BE Young receives no payment directly from Sanofi, and the trial is not for an influenza vaccine. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Key issues

• Emerflu is a candidate avian influenza pandemic preparedness vaccine, manufactured by Sanofi.

• The vaccine is an inactivated, split-virion formulation of 30 μg HA antigen with 600 μg of aluminum hydroxide adjuvant. Manufacture is modeled on the seasonal influenza vaccine Vaxigrip.

• Immunogenicity studies determined the vaccine was able to achieve adequate seroconversion rates in naïve children, adult and elderly populations. However, seroprotection rates in adults were consistently below CHMP criteria, and it was withdrawn from assessment by the EMA.

• Further studies of antibody persistence described a significant waning of antibody titers within 6 months of vaccination.

• Some evidence of boosting and cross-priming was available from the CHMP assessment report, but has not been published in peer-reviewed literature.

• Failure of this vaccine appears to be primarily a consequence of an insufficient immune stimulating effect by alum on subunit influenza vaccines.

• Emerflu has not been licensed by the FDA or EMA and additional clinical trials with the current formulation are not expected.