In mid January 2013 the United States regulatory authority for medicines, the Food and Drug Administration (FDA), declared its approval of a new vaccine for the prevention of seasonal influenza for people aged 18 to 49 years old.(1)
This particular vaccine employs a novel technology with an insect baculovirus virus expression system and recombinant DNA technology.(2) Hence the vaccine does not employ embryonated eggs or mammalian cell-lines as is common for all currently licensed influenza vaccines for growing the antigen. The new vaccine called Flublok, is produced by a company Protein Science.
Flublok is a recombinant trivalent influenza vaccine containing three, full length haemagglutinin proteins for intramuscular administration. The vaccine is designed to protect against two strains of influenza A, H1N1 and H3N2 as well as one influenza B strain (45 µg of each strain) following the yearly recommendations of health authorities.
The key study for the authorisation evaluated both efficacy and safety in adults during the 2007-2008 influenza season, enrolled 4648 healthy adults (mean age 32.5 years) randomized 1:1 ratio to receive a single dose of Flublok (n=2344) or saline placebo (n=2304).
The pre-defined success criterion for the efficacy analysis was that the lower bound of the 95% confidence interval of vaccine efficacy (VE) should be at least 40%. VE against antigenically matched culture-confirmed CDC-ILI could not be determined reliable because 96% of the influenza isolates obtained in this study were not antigenically matched to the strains represented in the vaccine. Using an exploratory analysis of vaccine effectiveness against all strains, regardless of antigenic match, isolated from any subject with ILI, not necessarily CDC-defined ILI, showed 44.8% (95% CI 24.4, 60.0) protective efficacy.
Unsolicited adverse reactions were collected 28 days post-vaccination and serious adverse events (SAE) were collected 6 months post-vaccination via clinic visit or telephone follow up on day 28 and 180 respectively or by spontaneous reporting.
The most common adverse reactions reported (>10%) were injection-site reaction including pain (>37%), headache (>15%), fatigue (>15%) and myalgia (>11%).
Immunogenicity was higher with HAI antibody responses of 72%, 81% and 52% against the A(H1), A(H3) and B viruses in adults 18-49 years receiving Flublok compared to other inactivated influenza vaccines.(3)
The safety and efficacy of Flublok have not been established in persons 50 years of age or older. In addition, Flublok has not been evaluated in pregnant or nursing women.
A randomized, controlled study in children 6 months to less than 3 years of age resulted in decreased hemagglutinin inhibition (HAI) responses compared to a US-licensed inactivated influenza vaccine approved for use in this age group. This strongly suggests that Flublok will not be effective in young children.Safety and effectiveness of Flublok in children 3 years to 18 years of age have not been established.
The FDA will continue to evaluate Flublok (5). Submission of pediatric studies for ages 3 years to <6 years and 6 years to <18 years are deferred until clinical studies are completed. The post marketing reporting requirements include establishing a pregnancy register to collect data prospectively in an actively recruited cohort of 600 women, of whom at least 300 will have been exposed to Flublok. Finally, an observational post-marketing safety study in approximately 25 000 Flubok recipients aged 18-49 years should be conducted to further characterize the safety profile using as a comparator as a US produced egg-based, trivalent inactivated influenza virus vaccine.
ECDC Comment, 29 January 2013:
A number of novel technologies are under development for new influenza vaccines.(3) The use of an insect baculovirus virus expression system and recombinant DNA technology is just one of many innovative approaches. However, the significance of this as a public health development is that this is the first innovative recombinant technology for influenza vaccines that has achieved licensure by a regulatory authority.
With Flublok production being independent of egg supply or mammalian cell availability, indicates a potential in accelerating the manufacturing process which can prove valuable in the event of a pandemic.
Flublok is not yet authorised in the European Union.
- US Food and Drugs Administration (FDA) approves new seasonal influenza vaccine made using novel technology
- Flublok Package insert
- Treanor JJ, El Sahly H, King J et al Protective efficacy of a trivalent recombinant hemagglutinin protein vaccine (FluBlok®) against influenza in healthy adults: A randomized, placebo-controlled trial Vaccine 2011; 29: 7733-7739
- Neuzil K, Bright R. Influenza Vaccine Manufacture: Keeping Up with Change JID 2009:200 (15 September) 835-7
- Food and Drug Administration, Post-marketing requirements BL 125285/0