Mucosal and systemic immunity correlates of protection against influenza in young children (MUSIC-Flu)

About this project

MUSIC-Flu is a prospective, non-interventional cohort study investigating how immune responses protect young children against influenza infection and illness. Influenza causes substantial illness and death globally, with a particularly high burden in sub-Saharan Africa. In South Africa, young children experience the highest infection rates and play a major role in transmission. While vaccines exist, their effectiveness is moderate, and the immune mechanisms that drive protection, especially those that reduce transmission, are not fully understood. This study focuses on identifying both systemic (blood-based) and mucosal (respiratory tract) immune markers that predict protection. Understanding these correlates is essential for improving vaccine design, accelerating evaluation of new vaccines, and informing immunisation strategies in similar settings. The study is being conducted in Jouberton, North West Province, among healthy children aged 2–5 years. Recruitment began in March 2026, with participants enrolled through local clinics. Children are followed intensively throughout the influenza season, with active follow-up from April to October 2026. This includes frequent nasal swab collection to detect infection, regular symptom monitoring, and repeated collection of blood and mucosal samples to measure immune responses over time. By combining detailed clinical follow-up with high-resolution immunological data, MUSIC-Flu provides a unique opportunity to understand how immunity develops, wanes, and protects against infection, illness, and onward transmission in a high-burden setting.

Objectives

Primary objectives:

Characterise mucosal and systemic immune responses in children with and without influenza infection
Identify immune profiles associated with influenza illness
Assess how immune responses influence viral load and duration of shedding

Secondary objectives:

Determine whether immune markers linked to protection against infection also protect against illness
Assess the impact of co-infections (e.g. RSV, SARS-CoV-2) on disease severity and immune responses
Measure how immunity wanes over time and estimate the durability of immune markers
Evaluate immune boosting and seroconversion following infection
Use mathematical modelling to define optimal vaccine profiles for reducing transmission
In a subset, examine how cellular immunity (e.g. CD4+ and CD8+ T cells) relates to protection and viral dynamics

Impact

MUSIC-Flu will generate critical evidence on how immunity to influenza functions in young children, particularly at the site of infection in the respiratory tract. The findings will support the development of more effective influenza vaccines, including those that reduce transmission, and inform regulatory pathways by identifying improved immune correlates of protection. In addition, the study will guide vaccination strategies in South Africa and other low- and middle-income settings, contributing to efforts to reduce the overall burden of influenza, especially among vulnerable populations. Ultimately, this work will help bridge key knowledge gaps needed to strengthen influenza prevention in high-burden settings.