Milestone in infant health: unveiling the RSV vaccine’s shielding effect for newborns

Introduction

Respiratory syncytial virus (RSV) stands out as a crucial pathogenic infection during childhood and is linked to substantial morbidity and mortality. Globally, it is estimated that RSV causes ~33 million new cases of acute lower respiratory tract infections (LRTIs) in children under 5 years of age, resulting in 3.6 million hospitalizations and around 100 000 RSV-related deaths annually. A staggering 97% of these deaths occur in low- and middle-income countries, making RSV the second-leading cause of infant mortality¹. Virtually all infants contract RSV by the age of 2, with reinfections persisting throughout life, albeit with reduced severity. Older adults, however, also face an elevated risk of developing a more severe illness during an RSV infection. Particularly concerning is its disproportionate impact on infants in low- and middle-income countries, where RSV ranks as the second-leading cause of infant mortality². Despite the existence of naturally acquired maternal antibodies, severe RSV-associated lower respiratory tract illness notably peaks within the first several months of life³. In addressing this phenomenon, maternal immunization emerges as a pivotal public health imperative, protecting against certain infections for both the mother and the child. Administering vaccines to pregnant women strategically induces vaccine-specific antibodies, facilitating their transplacental transfer or transmission to the infant through breastfeeding. This approach ensures heightened levels of immune protection for infants immediately after birth and in their early months of life⁴. The CDC’s recommendation for the first RSV vaccine for pregnant individuals is significant because it offers the potential to induce passive immunity in newborns, protecting them from RSV-associated respiratory disease. The RSVpreF vaccine has demonstrated efficacy in reducing medically attended severe RSV-associated lower respiratory tract illness in infants, with a vaccine efficacy of 81.8% within 90 days after birth and 69.4% within 180 days after birth⁵.

Understanding RSV: a silent menace

Most RSV infections in infants manifest as mild upper respiratory tract illnesses or ‘flu-like’ symptoms often accompanied by otitis media. Severe acute lower respiratory infections (ALRI) are predominantly observed in infants under 6 months of age. These severe infections result in bronchiolitis, pneumonia, and croup. Infants, individuals with preexisting cardiopulmonary conditions, the immunocompromised, and older adults are at a heightened risk of developing a more severe illness⁶. The current treatment options for RSV are limited, primarily focusing on supportive care. Ribavirin is the sole FDA-approved drug for the treatment of severe respiratory infections caused by RSV. However, its clinical use is restricted due to its high cost, lack of specificity, and limited symptom control⁷. Recognizing the inadequacy of available treatments, there has been an increased emphasis on RSV prophylaxis. A significant breakthrough in RSV prevention occurred with the development of the anti-RSV monoclonal antibody palivizumab, demonstrating that high-titer neutralizing antibodies can markedly reduce severe RSV disease⁸. Unfortunately, the necessity for monthly injections and associated costs limited its application as a universal strategy for preventing RSV in all infants. More recently, a new monoclonal antibody, nirsevimab, has received approval. Norseman offers two critical advantages over palivizumab: higher neutralization activity of the antibodies and an extended half-life. This means that a single pre-seasonal dose is adequate to protect high-risk infants, making nirsevimab a more cost-effective option⁶.

The game changer: Pfizer’s bivalent RSVpreF vaccine

Despite continuous efforts over several years, vaccine development has been challenging because an infant’s immune system is still immature in the early months of life and adjusting to the new environment⁹. Nevertheless, Pfizer’s bivalent RSVpreF vaccine, ABRYSVO, has recently received breakthrough FDA approval. This approval allows for active immunization of pregnant individuals from 32 to 36 weeks of gestational age, aiming to prevent lower respiratory tract infections caused by RSV in infants from birth up to 6 months¹⁰. ABRYSVO, previously approved for older adults, now stands as the first FDA-approved RSV vaccine for infants, marking a significant milestone in RSV prophylaxis during the early months of life, when infants face the most significant risk of severe consequences from RSV. ABRYSVO is an unadjuvanted and protein-based bivalent vaccine with two preF proteins carefully chosen to optimize protection against RSV A and B strains¹¹. The administration of a single dose of RSVPreF to pregnant women at the beginning of their third trimester resulted in the induction of neutralizing antibodies and the efficient transplacental migration of these antibodies to the developing fetus. Maternal vaccination effectively reduces the risk of acute lower respiratory infections and protects infants from RSV infection during the first 6 months of life⁵.

The implications and future prospects

RSV poses a substantial threat to global infant health, and current treatment options for RSV-associated LTRI are limited. Palivizumab, a humanized monoclonal antibody, has demonstrated a reduction in hospitalization rates when used preventively. However, the use of palivizumab is restricted to a narrow subset of high-risk infants, and its efficacy demands multiple doses¹². These limitations emphasize the critical need for alternative options. The emergence of the RSVpreF vaccine presents a promising avenue for mitigating these challenges. The RSVpreF vaccine exhibits notable efficacy in reducing medically attended severe RSV-associated lower respiratory tract illnesses within the first 90–180 days after birth⁵. This suggests its potential to improve short-term health outcomes for infants significantly. By preventing severe RSV infections, the vaccine can potentially reduce hospitalizations and medical interventions, offering substantial long-term health benefits for infants and their families. In 2017, the global cost of managing inpatient and outpatient cases of respiratory syncytial virus (RSV)-associated lower respiratory tract infections (ALRI) in young children was estimated at ~€4.82 billion. Notably, 65% of these costs were borne by developing countries, with hospitalization constituting 55% of the overall economic impact¹³. Implementing the RSVpreF vaccine could alleviate the financial strain on healthcare systems by reducing the demand for costly medical interventions. This, in turn, could lead to a more efficient allocation of resources, decreased healthcare costs, and enhanced financial stability for families. Particularly in low- and middle-income countries, where RSV remains a pervasive health challenge, the vaccine could represent a transformative tool in promoting sustainable healthcare practices. Future research on RSV prevention and treatment should focus on assessing the long-term efficacy and safety of the vaccine, particularly in high-risk populations. Exploring combination vaccines targeting multiple respiratory pathogens and alternative formulations with distinct adjuvants could further enhance efficacy and streamline immunization schedules. Continuous surveillance remains crucial for understanding RSV epidemiology and identifying gaps in prevention and treatment strategies.

Overcoming hurdles and ensuring access

The financial burden associated with RSV poses a significant challenge in terms of healthcare expenses, particularly in low- and middle-income countries¹⁴. Overcoming the obstacle of conspiracy beliefs related to medicine is a considerable challenge for vaccination programs, necessitating proactive strategies to combat misinformation¹⁵. There is observed hesitancy among pregnant women to receive vaccination, primarily driven by safety concerns. This underscores the importance of addressing factors influencing vaccine acceptance within this demographic. Enhancing acceptance and uptake of the RSV vaccine during pregnancy and infancy can be achieved through educational campaigns communicating its significance. It is crucial to address concerns regarding potential side effects of the RSV vaccination for pregnant women, as well as fears of harm to the fetus and general safety concerns. Collaborative efforts involving governments, nonprofit organizations, and pharmaceutical companies can lead to cost-sharing initiatives, making the vaccine more financially accessible. Coordinated global endeavors are essential to tackle disruptions in vaccine supply chains and ensure fair distribution. International organizations and governments can play pivotal roles in facilitating and fostering such collaborations.

Conclusion

To sum up, the recent approval of Pfizer’s bivalent RSVpreF vaccine, ABRYSVO, represents a significant advancement in pediatric health, particularly in the fight against RSV. RSV is a severe hazard to world health, especially for infants in low- and middle-income nations, where it is the second most common cause of infant death. Effective prevention is urgently needed because of the shortcomings of current therapies and the high cost of severe RSV infections. When given to expectant mothers, the RSVpreF vaccine shows impressive effectiveness in avoiding severe lower respiratory tract infections linked to RSV in infants during the crucial early months of life. With the vaccine’s approval, RSV prevention will advance significantly and have a more affordable option than the current monoclonal antibody treatments. The vaccination offers enhanced protection for high-risk newborns with a single pre-seasonal dosage, making it a feasible and affordable option. The RSVpreF vaccination has long-term effects that go beyond immediate health results. The vaccination may lessen hospitalizations, lessen the financial strain on healthcare systems, and improve the long-term health benefits for infants and their families by reducing severe RSV infections. Managing RSV-associated illnesses in young children comes at a significant financial burden worldwide, with developing nations bearing a disproportionate share of this burden. A new era of sustainable healthcare practices that results in more effective resource allocation and lower healthcare expenditures could be ushered in by introducing the RSVpreF vaccination.

Nonetheless, issues remain resolved, including ensuring equal access, vaccine hesitancy, and financial constraints in low- and middle-income nations. Proactive measures like educational campaigns and joint ventures between governmental bodies, nonprofits, and pharmaceutical firms are crucial to overcoming these obstacles. Coordinated global actions are essential to guaranteeing equitable distribution and resolving vaccine supply chain issues. As the RSVpreF vaccine shows promise in the fight against RSV, further studies should examine its long-term effectiveness, tolerability, and possible synergies with other respiratory pathogen vaccinations. Ongoing surveillance is still essential to comprehend RSV epidemiology and improve preventative and treatment approaches. The RSVpreF vaccination is opening the door for a healthier and more robust future for newborns globally as part of the ongoing effort to eradicate RSV-related morbidity and mortality.

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The authors have not received any funds.

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All authors have equally contributed to the manuscript and have approved the publication of the final manuscript.

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The authors declare that they have no financial conflicts of interest with regard to the content of this report.

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Guarantor

Zainab Nazir.

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Not commissioned, externally peer-reviewed.

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This is not a clinical trial.