Equity-by-design in RSV immunisation development

Background
Respiratory syncytial virus (RSV) infects nearly all children by age two, with reinfections common throughout life. While most infections cause mild upper respiratory symptoms, RSV can cause severe, potentially fatal lower respiratory tract infections in infants, particularly premature babies and those with comorbidities, with outcomes often worse in low- and lower-middle-income countries (LMICs) lacking adequate healthcare access.
Until recently, palivizumab (a short-acting monoclonal antibody, mAb) was the only approved preventive option, but its high cost limited use to high-risk infants. Nirsevimab (2022) became the first long-acting mAb approved for all infants, followed by a maternal RSV vaccine, and clesrovimab (2025). The WHO now recommends RSV prevention via maternal vaccination or mAbs, but LMIC implementation lags due to logistical and financial barriers and gaps in safety and efficacy data.
This thesis uses five research types across the translational spectrum to address inequities in infant RSV immunization access in LMICs: public health, basic, preclinical, clinical, and implementation research.

Key Findings:
Chapter 2 reviews the RSV vaccine/mAb landscape (as of June 2024: 5 marketed products, 30 in development), noting nirsevimab's >80% effectiveness against RSV hospitalization, while access remains concentrated in high-income countries despite LMICs bearing the greatest disease burden. Chapter 3 argues that access-to-medicine mechanisms (voluntary licensing, technology transfer) combined with WHO prequalification and funding mechanisms like Gavi are essential for affordable LMIC access.
Chapter 4 identifies barriers and facilitators for maternal immunization in Soweto, South Africa, through co-creation workshops with healthcare workers, yielding recommendations on education, community awareness, reporting incentives, and improved medical record-keeping.
Chapters 5–7 describe developing and validating a dried blood RSV-neutralizing antibody assay (using samples from a Gates MRI RSM01 phase 1 trial), showing dried blood can replace serum in bioanalyses (R² > 0.95), and successfully transferring this assay to a Ghanaian laboratory, strengthening local research capacity.
Chapters 8–9 cover industry-independent development of intranasal palivizumab drops. A phase 2b RCT in late-preterm infants found daily intranasal dosing was safe but did not significantly prevent RSV infection (38.3% vs 23.4% placebo). A controlled human infection model study in adults showed no reduction in viral titer despite a 72% reduction in symptomatic infections, suggesting intranasal mAbs are unlikely to be a viable, cost-effective protection strategy.
Chapter 10 evaluates mAb-resistant mutants (MARMs) under suboptimal antibody pressure for palivizumab, nirsevimab, and RSM01, finding RSM01 has a higher resistance barrier and that resistance generally reduces viral fitness, making global dominance of resistant strains unlikely.

Discussion
The thesis argues that current RSV product development follows a "trickle-down" approach designed for high-income contexts. It proposes an equity-by-design framework built on three lessons (begin with the end in mind, simplify methods for LMIC contexts, embed affordability early) and four recommendations: scientific co-ownership with LMIC partners, operational investment in local capacity, economic feasibility built in from early development, and social integration with community priorities—positioning equity as a foundational principle rather than an afterthought in RSV immunization development.