Innovative Approaches in RSV Prevention: The Expanding Role of Monoclonal Antibodies in Protection for All Infants

Abstract

Respiratory syncytial virus (RSV) continues to be a predominant cause of lower respiratory tract infections among infants and toddlers, posing a substantial burden on pediatric health and healthcare systems worldwide.

Introduction

Respiratory syncytial virus (RSV) continues to be a predominant cause of lower respiratory tract infections among infants and toddlers, posing a substantial burden on pediatric health and healthcare systems worldwide. According to international and European data, nearly 90% of children are exposed to RSV by the age of two years old [1]. Importantly, the infection’s severity is unpredictable, and no specific antiviral treatment is currently approved. Furthermore, hospitalizations associated to RSV infection may require advanced medical care, including oxygen therapy, mechanical ventilation, and intensive care unit support.

RSV contributes to 50-80% of acute bronchiolitis cases and approximately 31% of pneumonia cases in children [2,3]. Overall, RSV is responsible for over 33 million acute respiratory episodes annually and more than 118,000 deaths globally [4].

A recent analysis shows that Romania ranks 6th in Europe for RSV hospitalizations in infants under 1 year old and remains among the top countries for children under 5 years old, indicating an incidence well above the European average [5].

Monoclonal antibodies in RSV prevention: from high-risk groups to universal coverage

Currently, in Romania, passive prophylaxis against RSV infection relies on one of two types of monoclonal antibodies, each with distinct indications and characteristics. Conventional monoclonal antibodies (palivizumab) are reserved for high-risk infants, such as those born prematurely or with congenital conditions. These require monthly administration over a 5-month period during the RSV season [6]. In contrast, long-acting antibodies such as nirsevimab offer season-long protection with a single dose and are approved for use in all infants, regardless of risk status [7].

Monoclonal antibodies are among the most innovative solutions for preventing viral infections in newborns and infants, providing passive immunity from the moment of administration. A major advantage of this approach is the immediate protection conferred to the newborn, independent of maternal immunological status.

Nirsevimab: a long-acting monoclonal antibody for broad infant protection

Nirsevimab targets the RSV fusion protein, preventing viral entry and replication. Its engineered Fc region extends its half-life, allowing for full-season protection following a single dose [7].

These features have led to its recognition and approval by major international health authorities, including the European Medicines Agency (EMA) [8] and the United States of America (USA) Food and Drug Administration (FDA) [9], and its inclusion in national immunization programs in countries such asFrance [10], Spain [11], Germany [12], Italy [13], Belgium [14], Canada [15], USA [9], and the United Kingdom [16].

The demonstrated efficacy of nirsevimab in randomized clinical trials (RCTs), combined with validation through real-world evidence (RWE) studies, highlight its significant clinical and epidemiological benefit, reflected in a substantial reduction in RSV-related pediatric hospitalizations, supporting its inclusion into national immunoprophylaxis policies.

Evidence from clinical trials and real-world data

Summary of data from randomized clinical trials

RCTs provide a rigorous framework for evaluating efficacy under ideal, controlled conditions and are considered the gold standard in clinical research. Clinical trials, including phase 2b [17] and phase 3 (MELODY) [18], demonstrated nirsevimab’s efficacy in reducing RSV-related hospitalizations by 76.8% (95%CI: 51.9-90.3%)–78.4% (95%CI: 49.4-89.4%), with consistent results across both preterm and full-term infants. The HARMONIE Phase 3b study [19] confirmed 83.2% (95%CI:67.8-92.0%) efficacy in preventing lower respiratory tract infections caused by RSV.

Summary of real-world evidence

Following the implementation of immunization campaigns during the 2023/24 season, collected data reflect the performance of nirsevimab in clinical practice, offering valuable insight into its real-world public health impact. RWE confirm the high effectiveness of nirsevimab in preventing RSV-related hospitalizations under routine medical practice conditions. In Spain, efficacy in reducing hospitalizations due to confirmed RSV infections in infants was 82.0% (95%CI: 65.6-90.2%) [20]. In Chile, efficacy against RSV-associated acute lower respiratory tract infections hospitalizations was 76.4% (95% CI:72.57-79.72%), and 84.9% (95% CI: 79.47–88.95%) for intensive care unit admissions [21]. These findings validate the effectiveness of universal prophylaxis in clinical practice.

Public health impact of universal immunization with nirsevimab in the 2023/24 season

Spain recorded an 89.8% reduction in hospitalizations for confirmed RSV infections in infants compared to the previous year, with a number needed to immunize (NNI) of 25 (IQR 24–32) [20]. Chile’s universal immunization strategy with nirsevimab was associated with an estimated77.46% reduction in RSV-related pediatric hospitalizations, preventing 30 hospitalizations per 1,000 immunized infants, with an NNI of 35 [21].

Nirsevimab currently represents the most robust real-world prophylactic intervention for reducing RSV-related hospitalizations across all infant populations. Data from national immunization programs in Spain and Chile during the 2023/24 RSV season demonstrate substantial effectiveness of universal administration of this long-acting monoclonal antibody [20,21]. These findings reinforce the strategic value of long-acting monoclonal antibodies in public health approaches for RSV prevention, supporting their use as a preferred option for protecting all infants and young children.

Conclusions

Long-acting monoclonal antibodies represent a major innovation in RSV prophylaxis, offering immediate and long-lasting protection to all newborns and infants through a single administration per season. The effectiveness of this intervention is supported by both RCTs and RWE, which highlight significant reductions in hospitalizations and the burden on healthcare systems.

In this context, passive immunization with monoclonal antibodies is justified as a strategic component of national programs for the prevention of RSV respiratory infections in infants and young children.

Passive prophylaxis with long-acting monoclonal antibodies provides individual protection for infants and may also contribute to reducing community transmission and mitigating the socio-economic impact associated with severe respiratory infections.

This immunization strategy aligns with the recent recommendations of the World Health Organization, which supports the integration of RSV immunization, including long-acting monoclonal antibodies, into national programs, considering the global burden of RSV infection in infants and the demonstrated efficacy of these interventions [22].

Given the significant impact of RSV infection on infants and young children, as well as the robust scientific evidence supporting the effectiveness of modern prophylactic interventions, the Romanian Society of Pneumology and the Romanian Society of Infectious Diseases and HIV/AIDS jointly recommend the following:

(1) The implementation of scientifically validated RSV prevention strategies is essential to reduce the incidence of severe lower respiratory tract infections, hospitalizations, and associated complications in neonates and infants.

(2) The incorporation of long-acting monoclonal antibodies into national RSV prophylaxis programs represents a safe, effective, and operationally feasible approach to protecting all infants, irrespective of gestational age, comorbidities, or birth timing relative to the RSV season.

(3) Nirsevimab has the most extensive clinical experience currently available for protecting all newborns and infants, regardless of gestational age, comorbidities, or timing of birth relative to the RSV season, significantly contributing to the reduction of severe disease incidence and related hospitalizations.

(4) Prioritization of continuous and universal protection against RSV, which is essential for the entire pediatric population, given the universal exposure and the potential for any infant to develop complications, including severe forms of the disease. Monoclonal antibodies such as nirsevimab provide robust passive protection, independent of transplacental antibody transfer, offering immediate and long-lasting immunological coverage regardless of the timing of birth.