Imiquimod and Influenza Vaccine for Immunocompromised Patients (IMIFLU)

Safety and Immunogenicity of Seasonal Influenza Vaccine With Topical Imiquimod in Immunocompromised Patients: A Randomized Controlled Pilot Trial

In this open label, single centre, pilot randomized controlled clinical trial the investigators aim to compare the immunogenicity and safety of a new influenza vaccination strategy consisting in the topical administration of imiquimod at the injection site before vaccination vs. a standard intramuscular vaccine injection in SOT recipients and HIV-infected individuals. The investigators planned to enroll 70 outpatients patients (50% solid-organ transplant recipients and 50% HIV-infected patients) regularly followed at the Transplantation center and the Infectious disease outpatients' clinics of the Lausanne University Hospital. Study participants will be randomized in a 1:1:1 ratio to receive the standard intramuscular vaccine (control group) or a topical application of an imiquimod containing cream followed by intramuscular (imiquimod-IM) or intradermal (imiquimod-ID) vaccine injection. After vaccination participants will be followed for a period of 180 days. Blood samples will be drawn at baseline and at day 21 and 180 for assessment of immunogenicity. Safety outcomes will be assessed immediately after vaccine administration, and at day 7 (phone call), 21 and 180.

The control intervention consists in the administration of the standard intramuscular influenza vaccine (Mutagrip®), containing 15 μg of each of the three viral strains without imiquimod.

In the imiquimod and intradermal vaccine arm, intervention consists in the topical application of a single bag of Aldara™ creme 5%, containing 12.5 mg of imiquimod, on a 16 cm2 square delimitated area on the non-dominant arm at the time of influenza vaccination. An intradermal influenza vaccine preparations containing 15 μg of each of the three viral strains (Intanza®) will be administrated in the centre of the marked area after the imiquimod cream is fully absorbed.

In the imiquimod and intramuscular vaccine arm, intervention consists in the topical application of a single bag of Aldara™ creme 5%, containing 12.5 mg of imiquimod, on a 16 cm2 square delimitated area on the non-dominant arm at the time of influenza vaccination. An intramuscular influenza vaccine preparations containing 15 μg of each of the three viral strains (Mutagrip®) will be administrated in the centre of the marked area after the imiquimod cream is fully absorbed.

Vaccine response rate (=seroconversion rate) at day 21 is the proportion of participants exhibiting a fourfold or greater increase of anti haemagglutinin (anti-HA) antibodies from baseline, measured by haemagglutinin inhibition (HI) assay 21 days after vaccination, for at least one viral strain.

Seroprotection rates for each vaccine strain at baseline, and 21 and 180 days after vaccination. Seroprotection rate is defined as the proportion of patients exhibiting an anti-HA antibody titer of 1:32 or greater.

Inclusion Criteria: Provision of written, informed consent Age > 18 years HIV infection or at least 3 months after kidney transplantation Stable outpatients Able and willing to comply with the study protocol Exclusion Criteria: Documented egg and/or imiquimod allergy Previous life-threatening reaction to seasonal influenza vaccine (i.e. Guillain-Barré Syndrome) Previous severe reaction to imiquimod cream Pregnancy or breast-feeding Patients with autoimmune diseases For HIV-infected patients: Current active opportunistic infection For kidney transplant recipients: Ongoing therapy for rejection (including steroid pulse or prednisone > 2 mg/kg/day over more than 14 days) Ongoing therapy with IVIG and eculizumab or current and past (<6months) therapy with rituximab

Manuel O, Pascual M, Hoschler K, Giulieri S, Alves D, Ellefsen K, Bart PA, Venetz JP, Calandra T, Cavassini M. Humoral response to the influenza A H1N1/09 monovalent AS03-adjuvanted vaccine in immunocompromised patients. Clin Infect Dis. 2011 Jan 15;52(2):248-56. doi: 10.1093/cid/ciq104.

Cordero E, Manuel O. Influenza vaccination in solid-organ transplant recipients. Curr Opin Organ Transplant. 2012 Dec;17(6):601-8. doi: 10.1097/MOT.0b013e3283592622.

Manuel O, Humar A, Berutto C, Ely L, Giulieri S, Lien D, Meylan PR, Weinkauf J, Pascual M, Nador R, Aubert JD, Kumar D. Low-dose intradermal versus intramuscular trivalent inactivated seasonal influenza vaccine in lung transplant recipients. J Heart Lung Transplant. 2011 Jun;30(6):679-84. doi: 10.1016/j.healun.2011.01.705. Epub 2011 Mar 5.