Research article

Intradermal influenza vaccination of healthy adults using a new microinjection system: a 3-year randomised controlled safety and immunogenicity trial

Jiri Beran¹ , Arvydas Ambrozaitis² , Alvydas Laiskonis³ , Narseta Mickuviene⁴ , Patrick Bacart^5,6 , Yvan Calozet^5,7 , Etienne Demanet^5,8 , Stephane Heijmans^5,9 , Paul Van Belle^5,10 , Françoise Weber¹¹ and Camille Salamand¹¹

¹Vaccination and Travel Medicine Centre, Hradec Kralove, Czech Republic

²Department of Infectious Diseases, Dermatovenerology and Microbiology, Vilnius University, Vilnius, Lithuania

³Kaunas University of Medicine, Kaunas 2 Clinical Hospital, Kaunas, Lithuania

⁴Institute of Psychophysiology and Rehabilitation, Kaunas University of Medicine, Lithuania

⁵ResearchLink, a Clinical Trial Network of GPs, Thuin, Belgium

⁶General Practitioner, Private Practice, Molenbeek, Belgium

⁷General Practitioner, Private Practice, Gribomont, Belgium

⁸General Practitioner, Private Practice, Thuin, Belgium

⁹General Practitioner, Private Practice, Linkebeek, Belgium

¹⁰General Practitioner, Private Practice, Kraainem, Belgium

¹¹Sanofi Pasteur, Lyon, France

author email corresponding author email

BMC Medicine 2009, 7:13doi:10.1186/1741-7015-7-13

Published:	2 April 2009

Abstract

Background

Intradermal vaccination provides direct and potentially more efficient access to the immune system via specialised dendritic cells and draining lymphatic vessels. We investigated the immunogenicity and safety during 3 successive years of different dosages of a trivalent, inactivated, split-virion vaccine against seasonal influenza given intradermally using a microinjection system compared with an intramuscular control vaccine.

Methods

In a randomised, partially blinded, controlled study, healthy volunteers (1150 aged 18 to 57 years at enrolment) received three annual vaccinations of intradermal or intramuscular vaccine. In Year 1, subjects were randomised to one of three groups: 3 μg or 6 μg haemagglutinin/strain/dose of inactivated influenza vaccine intradermally, or a licensed inactivated influenza vaccine intramuscularly containing 15 μg/strain/dose. In Year 2 subjects were randomised again to one of two groups: 9 μg/strain/dose intradermally or 15 μg intramuscularly. In Year 3 subjects were randomised a third time to one of two groups: 9 μg intradermally or 15 μg intramuscularly. Randomisation lists in Year 1 were stratified for site. Randomisation lists in Years 2 and 3 were stratified for site and by vaccine received in previous years to ensure the inclusion of a comparable number of subjects in a vaccine group at each centre each year. Immunogenicity was assessed 21 days after each vaccination. Safety was assessed throughout the study.

Results

In Years 2 and 3, 9 μg intradermal was comparably immunogenic to 15 μg intramuscular for all strains, and both vaccines met European requirements for annual licensing of influenza vaccines. The 3 μg and 6 μg intradermal formulations were less immunogenic than intramuscular 15 μg. Safety of the intradermal and intramuscular vaccinations was comparable in each year of the study. Injection site erythema and swelling was more common with the intradermal route.

Conclusion

An influenza vaccine with 9 μg of haemagglutinin/strain given using an intradermal microinjection system showed comparable immunogenic and safety profiles to a licensed intramuscular vaccine, and presents a promising alternative to intramuscular vaccination for influenza for adults younger than 60 years.

Trial registration

Clinicaltrials.gov NCT00703651.