Monoclonal antibodies (mAbs) have revolutionized medicine, providing innovative treatments for many diseases. For decades, mAbs have increasingly become pivotal in paediatric care. Eculizumab has revolutionised atypical haemolytic uremic syndrome (HUS) treatment while palivizumab has significantly reduced hospitalizations from respiratory syncytial virus (RSV) in high-risk infants and children. The newly approved long-acting RSV mAbs nirsevimab and clesrovimab are now poised to extend and broaden this impact.

Despite their therapeutic efficacy, the widespread impact of mAbs, particularly in children has been hindered by barriers to global access. Using lower doses of mAbs for children (while essentially using the same formulations as adults) should reduce costs, pioneer greater access and lead to greater impact; however, infants and children remain neglected or suffer delays in access due to slow ethical approval, trial recruitment challenges and other issues. This is exemplified by the differential global availability of RSV mAbs and the lack of supply for many antitoxin antibody products for children such as for diphtheria where replacement mAbs offer an alternative, safer therapy yet investment remains insufficient.

Innovations in biotechnology are fostering efforts to make mAbs more accessible. Promising developments include reduced costs approaching vaccine-like pricing, non-inferiority of subcutaneous versus intravenous administration that may increase uptake in children (e.g., pembrolizumab data for childhood cancers) and a burgeoning, albeit early, pipeline of mAbs for the prevention and treatment of infectious diseases like malaria and HIV which particularly affect children. There have also been setbacks, such as with the revocation of EMA's and MHRA's approvals of crizanlizumab for sickle cell disease treatment amid limited clinical trial data from most-affected populations, such as in Africa.

This Frontiers in Pediatrics Research Topic aims to capture the currently unmet and future potential of mAbs on pediatric practice by analysing their past and present utilization, assessing their impact, and examining opportunities lost (or at risk) due to clinical development challenges, registration, and access limitations. The Research Topic strives to envision the potential uses of mAbs in child health and trace the ongoing R&D mAb development efforts dedicated to addressing childhood diseases, particularly those affecting underserved pediatric populations. Lastly, the Research Topic aims to explore how specific pathfinder pediatric mAbs could pave the way for enhanced global accessibility, demonstrating that low-dose, affordable mAbs can be broadly implemented, particularly in low- and middle-income countries.

To gather further insights into the role and pathway to impact of mAbs in pediatric global health, this Research Topic welcomes contributions that examine the topics outlined below. Contributions that explore pediatric mAbs in any context are welcome, although the series will aim to particularly focus on applications in low- and middle-income countries. The types of papers that will be considered include (but are not limited to):
• Innovations in lower-cost mAbs development and production, including costs of goods efficiencies, given low doses in children offer an initial route forward for LMIC access;
• Technological advancements in mAb formulations, routes of administration, presentation, supply chain, and delivery (including target product profile aspects to product design, such as the use of auto-disable syringes), with emphasis on resource-limited settings, and targeting pediatric use;
• Development of novel mAbs for infectious diease (e.g., gastrointestinal and respiratory) including for maternal administration with a view to protecting the foetus (e.g. Lassa fever or preventing mother to child transmission of HIV). Also non-communicable (e.g., childhood cancers, and haematology, rheumatology, and kidney diseases), and other (including rare) pediatric diseases, including the complementary role of mAbs with other modalities (including a review of the pediatric mAb pipeline);
• Opportunities (e.g., pediatric-informed PK/PD modelling) and challenges (patient recruitment) of accelerating regulatory approval and use of mAbs in children which are already approved for use in adults; and considerations to accelerate pediatric applications of mAb candidates currently in development for adult use;
• Implementation case studies, including market intelligence, financing models, and cost-effectiveness studies exploring enabling price thresholds to support broad access, as well as case studies illustrating global access challenges and opportunities to streamline mAb accessibility worldwide with a focus on pediatric indications;
• The role of various stakeholders (including funders and donors) in nurturing an environment that addresses upstream (research and development) and downstream structural challenges to the implementation of mAbs for pediatric use in low- and middle-income countries and having real impact with tangible products progressing through the pipeline and into implementation;
• Opportunities and efficiencies for vaccine-like pediatric mAb candidates stemming from the interplay between pediatric and/or maternal vaccines in development, complementary antibody correlates of protection research; and the role of mAbs given the increasing challenge of rising vaccine hesitancy;

This Research Topic is open to a broad range of article types, including systematic reviews, opinion articles, and original research (including clinical studies). Submissions on emerging mAbs, like long-acting RSV, HIV and malaria preventive therapies, more ambitious use of mAbs for pediatric unmet need (e.g. AMR and neonatal sepsis) and essential discussions on global access challenges and opportunities across pediatric applications are particularly encouraged.

Topic Editor Dr. Lindsay Keir works for Impact Global Health Limited which is a not-for-profit research and policy organisation. Topic Editor Dr. Peter Gardner is currently Scientific Director in the global health team at LifeArc. LifeArc is a self-funded, not-for-profit life science organisation which collaborates, funds, and carries out scientific research to ensure great science achieves its potential and reaches patients faster. This includes the discovery, development, and humanisation of monoclonal antibodies (mAbs) and providing R&D funding to tackle technical barriers to mAb affordability to increase global access and drive public health impact. Topic Editor Dr. Sébastien Morin works for the Medicines Patent Pool, a not-for-profit foundation that has prioritised several monoclonal antibodies (mAbs) for in-licensing as the first step towards working with biosimilar manufacturers to reduce the prices of such prioritised mAbs and increased their access for populations in low- and middle-income countries.

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Maximizing the Global Impact of Monoclonal Antibodies for Children