The purpose of the study is to evaluate innate and adaptive immunity following QIV-HD vaccination compared to QIV-SD vaccination in people 65 years of age and older.

The hypothesis is that higher dose of antigen can increase the intensity and the quality of innate immunity, as the adaptive humoral and cellular responses.

In this study, the objectif is to evaluate innate and adaptive immunity following QIV-HD vaccination compared to QIV-SD vaccination in people 65 years of age and older.

Modifications of early blood molecular (transcriptome) and cellular (blood phenotyping) signatures within the first 24 hours following vaccination will be investigated. The association between early gene signature and late influenza-specific humoral immune responses weeks/months after vaccination will be also assessed.

This study is a hase IV, randomized, open-label, active-controlled, multi-center study comparing the immune response induced by QIV-HD vaccine (intervention) and QIV-SD vaccine (control).

Inclusion Criteria:

1. Aged 65 years or older, the day of inclusion;
2. Have signed and dated Informed Consent Form;
3. Able and willing to attend all scheduled visits, and to comply with study procedures;
4. Covered by French health insurance.

Non-Inclusion Criteria :

1. Any vaccine injection (including COVID-19 vaccine) in the 4 weeks preceding study inclusion;
2. Plan to receive any vaccine (including COVID-19 vaccine) in the 4 weeks following study inclusion;
3. Already vaccinated against influenza for 2021-2022 season;
4. Hypersensitivity to any of the vaccine components, or history of a life-threatening reaction to the vaccines used in the study or to a vaccine containing any of the same substances;
5. HIV infection;
6. Active Hepatitis B, or active Hepatitis C;
7. Previous Guillain Barré syndrome;
8. Ongoing immunosuppressive treatment or active immunodeficiency;
9. Receipt of immune globulins, blood or blood-derived products in the past 3 months;
10. Thrombocytopenia or bleeding disorder, receipt of anticoagulants contraindicating IM vaccination based on investigator's judgment;
11. Influenza-like illness symptoms, including COVID-19, within 4 weeks before study inclusion;
12. Personnes referred to in articles L1121-6 and L1121-8 of Public Health Code (persons deprived of liberty by judicial or administrative decision and persons subject to a legal protection measure: guardianship or curatorship).

Exclusion Criteria:

1. Any subject presenting with influenza-like illness symptoms, including COVID-19 between inclusion (visit 1) and randomization (visit 2);
2. Subject unable to attempt visit at Day 0 (visit 2) and Day 1 (visit 3);
3. Blood sample at Day 0 (visit 2) impossible to obtain;
4. Receipt of vaccine injection or equivalent between inclusion (visit 1) and randomization (visit 2), other than those allowed and planned in the study. This includes non-study dose of 2021-2022 influenza vaccine, blood-derived immune globulins, blood, or blood-derived products.
5. Any unexpected event relevant to the physician in charge, after discussion with the coordinating investigator and the sponsor