Safety and efficacy of a novel microneedle device for dose sparing intradermal influenza vaccination in healthy adults.

BACKGROUND: Intradermal vaccine delivery has been shown to induce good immune responses with low vaccine doses. Technologies for drug-delivery which specifically target the skin may render intradermal vaccination more accessible.

METHODS: We conducted a prospective, randomized trial in 180 intended-to-treat healthy adults. Study objectives were to evaluate the safety and immunogenicity of low-dose intradermal (ID) influenza vaccines delivered using a novel microneedle device (MicronJet). This device replaces a conventional needle, and is designed specifically for intradermal delivery. Subjects were randomly assigned to receive either the full-dose standard flu shot (containing 15 microg hemagglutinin per strain) delivered intramuscularly using a conventional needle (IM group), a medium dose intradermal injection (6 microg hemagglutinin per strain) delivered with the MicronJet (ID2 group), or a low-dose intradermal injection (3 microg hemagglutinin per strain) delivered with the MicronJet (ID1 group). A marketed influenza vaccine for the 2006/2007 influenza season (alpha-RIX by GSK Biologicals) was used for all injections. Adverse events were recorded over a 42-day period. Immunogenicity was evaluated by changes in hemagglutination inhibition (HAI) antibody titer, and by comparing geometric mean titers (GMTs), seroconversion, and seroprotection rates between the study groups.

RESULTS: Local reactions were significantly more frequent following intradermal vaccination, but were mild and transient in nature. At 21 days after injection, GMT fold increase was 22, 18 and 22 in the ID1, ID2 and IM groups respectively for the H1N1 strain; 9, 9 and 16 for the H3N2 strain and 9, 13 and 11 for strain B. The CPMP criteria for re-licensure of seasonal influenza vaccines were met in full for all study groups.

CONCLUSIONS: Low-dose influenza vaccines delivered intradermally using microneedles elicited immunogenic responses similar to those elicited by the full-dose intramuscular vaccination. The microneedle injection device used in this study was found to be effective, safe, and reliable.