Mucosal and Systemic Immunity Correlates of Protection Against Influenza in Young Children, Aged 2-5 Years (MUSIC-Flu)

Title: Mucosal and systemic immunity correlates of protection against influenza in young children (MUSIC-Flu). The goal of this observational study is to better understand how immune responses in the blood and mucosa are linked to protection against influenza infection and illness in young children. We will compare immune responses in children who get influenza infection to those who do not. Children aged 2-5 years of age will be followed from April through October 2026 during the influenza season in South Africa. During this time, nasal swabs will be collected three times per week to test for influenza and other respiratory viruses. Information on symptoms and temperature will be collected by nurses at weekly visits and daily by caregivers using an electronic symptom diary. Blood samples will be collected before and after the influenza season, and at two additional time points during the study. Special immune cells will also be collected from blood samples before and after the season. In addition, samples from the nose and mouth will be collected every month. These samples will be tested to measure immune responses, including antibodies, signaling proteins (cytokines), and specific immune cells (T cells and B cells).

Inclusion Criteria: * Children aged 2-5 years of age (i.e. from the second birthday until 5 years and 11 months of age) at the time of enrolment. * Healthy children as established by medical history and clinical examination before entering the study. * Parent availability and willingness to provide written informed consent to all study procedures * Child planning to reside in the selected community for the duration of the study. Exclusion Criteria: * Presence of malnutrition (defined as z score for age \