Prevalence, Genetic Risk Factor and the Use of Intradermally-administered Inactivated Influenza Vaccine With Topical Imiquimod in Influenza Vaccine Non-responsive Children

This study is a cross-over randomized-controlled trial (RCT). The outline of the study is shown in Figure 1. This study is divided into two parts: (i) screening for vaccine non-responders; and (ii) RCT for vaccine responsiveness using second dose IIV-IM, IIV-ID or IIV-Q-ID.

Children and adolescents between 8 and 18 years old will be recruited through our network of primary and secondary schools that have participated the Seasonal Influenza Vaccination School Outreach Programme before the influenza vaccination campaign. Information sheets, a consent form and a health demographics form indicating that they fulfill the inclusion and exclusion criteria (see below) will be distributed to the parents through the participating schools. A study hotline will be available for parents to contact the study team to answer any enquiries.

In the health demographics form, apart from questions related to the inclusion and exclusion criteria, the study team will also enquire about the subjects' demographics, including birth, gender, past medical history, and body weight and height. Previous influenza vaccination history will also be sought, including age at receiving the first influenza vaccine, whether the subjects have received influenza vaccines in the last season and the type of influenza vaccines they received.

All subjects should be receiving 0.5ml IM quadrivalent IIV, which contains 15micrograms hemagglutinin of each influenza strain, through the Seasonal Influenza Vaccination School Outreach Programme. Consented subjects will have 5-10ml clotted blood and 3ml EDTA blood draw at day 21 post-vaccination at school by our outreach study team. The parents of all participating subjects will receive an incentive equivalent to HKD 100. They will also receive their influenza vaccine response results in concealed envelops distributed through the schools.

Post-vaccination HAI titer against the Influenza B Yamagata strain ≤10 will be considered as "preliminary no seroconversion". The same serum taken on day 21 post-vaccination will be further processed to confirm that their HAI titer against the other Influenza A H1N1 and H3N2 and Influenza B Victoria strains are also ≤10. MN assay for all four strains will also be performed as the baseline for the part 2 RCT.