Authors: Yu Mi Jo, Joon Young Song, In Sook Hwang, Jacob Lee, Sang Cheul Oh, Jun Suk Kim, Sung Ran Kim, Woo Joo Kim, Hee Jin Cheong. Dose sparing strategy with intradermal influenza vaccination in patients with solid cancer. Journal of Medical Virology; 81, 4; 722-727; 2009.

This study investigates the effectiveness of intradermal vaccination (as opposed to the standard intramuscular or subcutaneous routes) as one of a number of antigen sparing strategies that could be used in the event of vaccine shortage during a influenza pandemic. As an additional rationale The authors point out that, although the level of immunogenicity obtained by intradermal vaccination of healthy individuals has been experimentally evaluated, no studies have been conducted in patients with compromised health. This study was designed to evaluate the immunogenicity of an intradermal injection with one half the intramuscular dose of a commercial influenza vaccine in patients with solid cancer, and to assess any commoner adverse events from vaccination.

For the study, 113 patients with carcinoma of solid organs were recruited using informed consent and received the trivalent inactivated split vaccines (Fluarix, Glaxosmithkline and Germany), which included both 0.5 and 0.25 ml pre-filled syringe vaccines containing  15 and 7.5 micrograms of hemagglutinin antigens from each of three different strains of influenza virus (A/H1N1, A/H3N2 and B). A randomized study was carried out with 59 patients being vaccinated with a conventional dose of influenza vaccine by the intramuscular route in the upper arm region and while another 54 received influenza vaccination with one half the conventional dose via intradermal route in the forearm. All were observed for 30 min after vaccination to check for any immediate acute adverse reactions. On the 3rd and 7th days after the vaccination, each patient was asked through telephone interviews about occurrence of local or systematic reactions. Two serum samples were collected from each patient: a pre-vaccination sample immediately prior to the administration of the vaccine and a post-vaccination sample 4-6 weeks after the vaccination.

The investigators found no significant difference between the injection routes in the increase in the titre of antibodies to A(H1N1), A(H3N2) and B four to six weeks after the vaccination. There was a good serological ; response in around 70% of patients against all three influenza strains irrespective of the vaccination routes. No serious events were observed though local skin reactions were more frequent in the intradermal injection recipients than in the intramuscular recipients (32.7% versus 9.1%).

ECDC Comment

This small but encouraging study suggests that intradermal injection of one half the dose of a commercial influenza vaccine was as effective at protecting these patients with serious medical conditions as a fulldose of intramuscular vaccine. Statements on serious adverse reactions should be more cautious given the low numbers involved. Presumably an intradermal injection will be working by recruiting dendritic cells and macrophages in the skin as was presumed in another study using this technique with similar findings.(1)  One limitation of the study noted by the authors was that a half-dose intramuscular injection group was not included in the study (for ethical reasons). However it also needs to be appreciated that without automatic equipment the benefits of a doubling of the number of people that could be immunised have to be offset against the technical difficulty of undertaking intradermal, especially when needing to immunise large numbers of people at once. An additional conclusion is that, although half-dose intradermal vaccine seems to offer adequate immunogenicity, this needs to be compared to even smaller dosage of vaccine. Other strategies that are bing considered tp ‘stretch’ vaccines are the use of various adjuvanted formulations.(2)

1. Holland D, Booy R, De Looze F. et al Intradermal influenza vaccine administered using a new microinjection system produces superior immunogenicity in elderly.adults. A randomised controlled trial. JID 2008; 198:650-8.
2. Levie K, Leroux-Roels I, Hoppenbrouers K et al An adjuvanted, low-dose, pandemic influenza A(H5N1) vaccine candidate is safe, immunogenic and induces cross-reactive immune responses in health adults. JID 2008; 198: 642-9