Jonne Terstappen

Respiratory syncytial virus (RSV) is a common respiratory pathogen, first isolated in 1956. It is now recognized as the leading cause of lower respiratory tract infections (LRTI) in young children aged <5 years worldwide. Nearly all children are infected with RSV at least once by the age of 2 years. Severe disease primarily affects infants and older adults with comorbidities. The principle aim of this thesis is to use a multidisciplinary approach to reduce inequitable access to RSV immunisation for infants in low- and lower-middle income countries (LMICs). Five research types on the translational science spectrum were used in the pursuit of global RSV equity: public health research, basic research, preclinical research, clinical research, and implementation research. Part II focuses on global access. Chapter 2 reviews the RSV vaccine and monoclonal antibody (mAb) landscape, highlighting the risk of a vaccine gap between high-income countries and LMICs. Chapter 3 proposes public-health-oriented access mechanisms, such as technology transfers, to ensure affordable access to mAbs. Chapter 4 examines the barriers and facilitators to maternal immunisation in Soweto, South Africa, through stakeholder engagement. Part III demonstrates how simplicity can enable inclusivity. Chapters 5 and 6 present the development of an assay to measure RSV neutralising antibodies in dried blood, allowing for easier sampling in remote areas. Chapter 7 details the successful technology transfer of this assay to a laboratory in Ghana. Part IV covers the development of affordable mAbs. Chapters 8 and 9 describe trials of palivizumab nose-drops, which ultimately showed a lack of efficacy in preventing respiratory infections. Chapter 10 evaluates the risk of mAb resistant mutants, showing that the candidate mAb RSM01 has a high barrier to resistance. Part V concludes with a general discussion in Chapter 11, emphasizing that RSV immunisation equity requires a paradigm shift towards 'equity-by-design' principles, integrating affordability and accessibility into the development process from the start.