Bringing Preventive RSV Monoclonal Antibodies to Infants in Low- and Middle-Income Countries: Challenges and Opportunities

Abstract

Respiratory syncytial virus (RSV) is the leading cause of acute lower respiratory tract infections (LRTIs) in infants. Most deaths occur in infants under 3 months old, and those living in low and middle-income countries (LMICs). There are no maternal or infant RSV vaccines currently approved. An RSV monoclonal antibody (mAb) could fill the gap until vaccines are available. It could also be used when a vaccine is not given, or when there is insufficient time to vaccinate and generate an antibody response. The only currently approved RSV mAb, palivizumab, is too costly and needs monthly administration, which is not possible in LMICs. It is imperative that a safe, effective, and affordable mAb to prevent severe RSV LRTI be developed for infants in LMICs. Next generation, half-life extended mAbs in clinical development, such as nirsevimab, show promise in protecting infants against RSV LRTI. Given that a single dose could cover an entire 5-month season, there is an opportunity to make RSV mAbs affordable for LMICs by investing in improvements in manufacturing efficiency. The challenges of using RSV mAbs in LMICs are the complexities of integrating them into existing healthcare delivery programs and surveillance systems, both of which are needed to define seasonal patterns, and monitor for escape mutants. Collaboration with key stakeholders such as the World Health Organization and Gavi, the Vaccine Alliance, will be essential for achieving this goal.

Optimizing next-generation RSV prevention in Mali: a cost-effectiveness analysis of pediatric vaccination, maternal vaccination, and extended half-life monoclonal antibody immunoprophylaxis

“…A phase 3 trial of nirsevimab, an extended half-life mAb, showed 74.5% protection against RSV LRTI [36], slightly outperforming the Preferred Product Characteristics. However, this product has an anticipated price point suitable for high-income countries, and effectiveness of the biosimilar products under development may differ [9]. Third, our static model did not account for potential herd immunity effects of RSV LRTI prevention.…”

“…This increases logistic complexity and costs compared to the single-dose regimens expected for maternal vaccines and extended half-life mAbs. Finally, RSV vaccines may have lower efficacy during the first six months of life due to immune immaturity and interference from circulating maternal antibodies [9,12], a period coinciding with the highest RSV LRTI burden [13].…”

“…Alternatives to pediatric RSV vaccine strategies include maternal RSV vaccination, which would use antenatal care delivery platforms in need of strengthening in many LMICs [8], or extended half-life mAbs, a technology new to LMIC immunization programs. The most practical strategy for RSV prevention in LMICs would be pediatric RSV vaccination programs integrated into established routine immunization schedules, but there are also challenges to this approach [9]. First, pediatric RSV vaccine research and development lags behind that for maternal vaccines and extended half-life mAbs [10].…”

RSV Prevention in All Infants: Which Is the Most Preferable Strategy?

“…Palivizumab provided the proof of concept that mAbs can be used to prevent RSV disease, and there are ongoing efforts to produce mAbs that provide a more sustained protective effect against RSV than licenced mAbs ( 67 , 68 ). As such, several long-acting mAbs are in clinical development for RSV prophylaxis in infants, including at least four mAbs in early development and two in late-stage development (nirsevimab and MK-1654) ( 56 ).…”

WHO preferred product characteristics for monoclonal antibodies for passive immunization against respiratory syncytial virus (RSV) disease in infants – Key considerations for global use

“…Similar information is also not available for the other two mAbs in clinical development. Sponsors of all three mAbs have acknowledged the global burden of RSV, and the preponderance of RSV mortality in LMICs [6] .…”