Preventing RSV from Birth: The Power of Maternal Immunization.

Authors:
Felicitas Colombo, MPA
Enrique Chacon-Cruz, M.D., MSc

Prof. Susanna Esposito is Full Professor of Pediatrics at the School of Medicine of the University of Parma, Italy. She is President and Founder of the World Association for Infectious Diseases and Immunological Disorders (WAidid), a position she has held since 2014, and Chair of the Committee on Infectious Diseases of the Italian Society of Pediatrics

Prof. Esposito has held numerous leadership positions in pediatric infectious diseases and vaccination. She served as President of the Italian Society of Pediatric Infectious Diseases (SITIP) from 2011 to 2014 and has been a member of the Steering Committee on Vaccination of the Italian Society of Pediatrics and the Steering Committee on Vaccines of the Italian Society of Allergy and Immunology. She has also served as President of the WHO Committee for measles and rubella eradication and was Chair of the Vaccines Group of the European Society for Clinical Microbiology and Infectious Diseases (EVASG), and served on the European Society for Pediatric Infectious Diseases (ESPID) Steering Committee and its Training and Research Committees.

Her academic and editorial experience includes serving as International Editor of The Pediatric Infectious Disease Journal and as Associate Editor of several international journals, including BMC Infectious Diseases, Human Vaccines & Immunotherapeutics, and the Journal of Clinical Virology. She has also served on the Editorial Board of PLOS ONE.

Prof. Esposito’s research focuses on vaccines, respiratory tract infections, antimicrobial therapy, emerging infections, and preventive pediatrics. Her research has resulted in more than 500 publications in international peer-reviewed journals indexed in PubMed, with an h-index of 67.

Prevention

For Prof. Susanna Esposito, the value of vaccination begins with a simple principle: prevention must be designed around the children and health systems it is intended to protect.

“The essential lesson has been that prevention must be designed around real children and real health systems. It is not sufficient to develop an effective product. We must understand who is most vulnerable, communicate clearly with families, monitor safety carefully and ensure that protection reaches children, regardless of where they are born,” says Prof. Esposito reflecting on the lessons that have shaped her career.

A pediatric infectious disease specialist, researcher and advocate for immunization, Prof. Esposito has built her career at the intersection of clinical pediatrics, epidemiology, infectious diseases and vaccine research. Her work has included influenza, pneumococcal and meningococcal disease, pertussis, respiratory syncytial virus (RSV) and emerging respiratory viruses, as well as vaccine research involving premature infants, immunocompromised children and children with chronic diseases. Her international clinical experience, including work in Burundi, has also reinforced her perspective on health equity.

That philosophy is particularly relevant as the global health community enters a new era of RSV prevention, with both maternal vaccination and long-acting monoclonal antibodies providing opportunities to protect infants during the first months of life.

RSV: from seasonal bronchiolitis to a global health priority

RSV has long been recognized as an important cause of bronchiolitis and respiratory illness in young children. Increasing surveillance and improved diagnostic methods, however, have expanded our understanding of its global impact. In Prof. Esposito’s view, the shift has been significant.

“Our understanding has evolved from viewing RSV primarily as a seasonal cause of bronchiolitis to recognizing it as a major global health problem,” she points out.

RSV infection occurs widely in early childhood, and severe disease is not limited to premature infants or children with underlying medical conditions. Many hospitalized infants were previously healthy. It is estimated that RSV is associated with more than 3.6 million hospitalizations and approximately 100,000 deaths annually among children younger than five, with approximately half of deaths occurring during the first six months of life and the overwhelming majority occurring in low- and middle-income countries. 

The implications extend beyond the acute episode. Although the precise causal relationships remain under investigation, RSV infection in early life has been associated with recurrent wheezing, repeated respiratory illness and possible longer-term effects on lung health. 

“RSV prevention is therefore a public health priority because it can prevent severe disease precisely when infants are most vulnerable, reduce seasonal pressure on emergency departments and pediatric wards, and potentially narrow major global inequalities in infant survival,” declares Prof. Esposito.

Thus, the arrival of effective infant-protection strategies represents more than a new vaccine opportunity. It creates the possibility of changing how RSV is managed as a public health issue.

Maternal immunization: protection before birth

One of the most important developments in infant RSV prevention is the ability to protect babies before they are born.

Maternal immunization works by stimulating the mother’s immune response during pregnancy, allowing antibodies to cross the placenta and provide passive protection to the newborn. WHO now recommends either maternal RSV vaccination during the third trimester or a long-acting monoclonal antibody for infants, depending on the local context, feasibility, cost-effectiveness and expected coverage. 

“Vaccinating during pregnancy raises maternal antibody concentrations and allows protective antibodies to cross the placenta. The infant is consequently protected from birth without having to generate an active immune response during a period when the immune system is still immature,” Prof. Esposito describes the biological rationale.

Clinical evidence has demonstrated protection against severe RSV disease in infants following maternal RSV vaccination. The phase 3 MATISSE trial, for example, demonstrated significant efficacy of maternal RSVpreF vaccination against severe RSV-associated lower respiratory tract illness in infants. 

“Nevertheless, safety during pregnancy requires an especially rigorous standard,” Prof. Esposito notes.

Her comments are particularly relevant to the history of maternal RSV vaccine development where experience illustrates why pregnancy trials require careful monitoring and why regulatory decisions must consider both efficacy and safety signals throughout development and after authorization.

For Prof. Esposito, the challenge is not simply developing the vaccine. Timing, access and communication are equally important.

“The challenges include choosing the optimal timing, ensuring sufficient time for placental antibody transfer, reaching women who receive limited alternative care, overcoming vaccine hesitancy, and coordinating obstetric and pediatric services,” she acknowledges. “Communication is fundamental. Pregnant women must receive clear evidence-based information about both the benefits of vaccination and the risk RSV poses to their infants.”

Beyond RSV: building a portfolio of maternal and passive protection

RSV is not the first example of maternal immunization protecting infants. Influenza vaccination during pregnancy can protect both the pregnant woman and her infant, while pertussis vaccination during pregnancy is widely used to provide passive protection to newborns. COVID-19 vaccination during pregnancy also protects against severe maternal disease and can result in the transfer of antibodies to the newborn.

Looking ahead, Prof. Esposito sees opportunities beyond the vaccines already in use.

“For future innovation, human metapneumovirus is particularly interesting because it belongs to the same viral family as RSV and causes significant lower respiratory tract disease in young children,” she explains.

She also identifies parainfluenza viruses as potential targets and points to combination products and rapidly adaptable vaccine platforms as areas deserving attention. But she cautions against assuming that a single technology will solve every prevention challenge.

“The goal should be to create a flexible portfolio rather than assume that one technology will meet every need,” she advises.

That portfolio could include maternal vaccines, infant vaccines and long-acting monoclonal antibodies, deployed according to epidemiology, health-system capacity and the characteristics of individual populations.

Maternal vaccination or monoclonal antibodies? 

The emergence of long-acting monoclonal antibodies has added another dimension to infant RSV prevention. 

Unlike maternal vaccination, monoclonal antibodies provide the infant directly with passive immunity. They can be administered shortly after birth or before the RSV season and do not depend on the mother’s immune response or on transplacental antibody transfer. WHO recommends that countries consider either maternal vaccination or a long-acting monoclonal antibody according to local circumstances.

So which approach is better?

“There is no universal winner. The greatest benefit will come from the strategy that achieves the highest timely coverage in a particular population,” Prof. Esposito answers deliberately pragmatic.

Maternal vaccination offers protection from birth and can be incorporated into antenatal care. It may be particularly sustainable in settings where antenatal-care coverage is high.

Monoclonal antibodies, meanwhile, offer a standardized dose directly to the infant and can be particularly valuable for premature babies or infants whose mothers were not vaccinated, were vaccinated too close to delivery or did not mount an adequate immune response.

“A long-acting monoclonal antibody provides a standardized dose directly to the infant, acts rapidly, and does not depend on the mother’s immune response,” Prof. Esposito explains. “Monoclonal antibodies provide an essential complementary pathway for infants not adequately protected through pregnancy.”

The two approaches should therefore not necessarily be viewed as competitors. Instead, they can provide complementary pathways for protecting infants who might otherwise remain vulnerable.

This distinction is increasingly reflected in global policy. WHO currently recommends either maternal RSV vaccination or a long-acting monoclonal antibody for the same mother-infant pair, with exceptions for specific circumstances. 

The real challenge: implementation

For Prof. Esposito, scientific innovation alone is insufficient.

“The biggest barriers are price, financing, supply, and delivery infrastructure,” she shares when asked about the major obstacles to equitable RSV prevention in low- and middle-income countries.

These challenges are compounded by differences in diagnostic surveillance, oxygen availability, birth settings, RSV seasonality and access to antenatal care. For countries with the highest RSV mortality, introducing a new intervention therefore requires much more than regulatory approval.

“International financing, pooled procurement, target pricing, technology transfer, and expanded regional manufacturing,” Prof. Esposito emphasizes the list of needs for new interventions.

She also argues that RSV prevention should be incorporated into existing maternal and child-health systems rather than established as a completely separate programme. This is consistent with WHO’s current approach, which emphasizes country-specific decisions based on feasibility, cost-effectiveness, expected coverage and health-system capacity.

“Universal impact will depend as much on implementation and affordability as on scientific efficacy,” Prof. Esposito summarizes.

Regulation: innovation needs confidence

The same tension between innovation and implementation emerges when the conversation turns to the regulatory environment. Prof. Esposito anticipates continued development across several vaccine fields, including new pneumococcal conjugate vaccines, novel platforms, mRNA technologies, respiratory-virus vaccines and vaccines targeting diseases such as dengue. But she returns to the same central challenge.

“We have different products, but the problem is implementation. And the problem is represented by recommendation by public health authorities,” she proclaims.

For her, consistency in public-health recommendations matters because fragmented recommendations can affect public confidence.

“When these recommendations are homogeneous, then coverage is high. But, especially for political reasons in several countries, there isn’t an agreement or recommendations. And this creates vaccine hesitancy among the population,” Prof. Esposito warns.

The regulatory environment, therefore, cannot be separated from the broader policy environment. Scientific evidence may establish what a vaccine can do, but public-health authorities must translate that evidence into coherent recommendations, targeted programmes and effective communication.

Pregnancy requires rigor, not lower standards

Regulatory requirements for clinical trials in pregnancy are controversial. Some believe they should become less stringent to facilitate broader maternal immunization. For Prof. Esposito the answer is unequivocal.

“No, I think that in pregnancy the regulation of the affairs is very important. So it is very difficult to move forward without big clinical trials that assess safety,” she says.

Her position highlights an important principle: expanding maternal immunization does not mean lowering the evidentiary threshold. Rather, it means investing in the research, surveillance and communication systems necessary to generate confidence in vaccines during pregnancy.

That is particularly important as maternal vaccination becomes an increasingly relevant strategy not only for RSV but also for influenza, pertussis and potentially other infectious diseases.

Rebuilding awareness of vaccine-preventable disease

For Prof. Esposito, one of the greatest challenges facing immunization today is paradoxically a consequence of its success.

“I think that it is very important to speak about the risk of vaccine preventable diseases, because usually we say that the problem of vaccines is represented by their success,” she confides.

When diseases become rare, the memory of their consequences can fade. That can make the benefits of vaccination less visible while concerns about vaccination remain highly salient.

Her message is therefore not simply about developing new vaccines but also about preserving public understanding of why existing vaccines remain necessary.

Looking ahead: an integrated life-course approach

Prof. Esposito envisions respiratory-virus prevention over the next decades and describes a future in which different technologies work together.

“I envisage an integrated life-course approach beginning before birth,” she envisions.

In this model, vaccination during pregnancy could protect both mother and infant; long-acting monoclonal antibodies could protect infants who are not adequately covered through maternal vaccination; and future active infant vaccination could extend protection later in life. She also sees potential in multivalent products targeting more than one respiratory pathogen.

But innovation must remain evidence-driven. New combinations and platforms will need to demonstrate safety, immunogenicity, affordability and practicality, while surveillance systems will need to evolve alongside them.

“Most importantly, innovation must be accompanied by equitable access,” Prof. Esposito emphasizes adding her proposed measure of success. “Our success should not be measured only by how many [available] products with licenses, but by how many hospitalizations, deaths, and lifelong respiratory complications we are preventing in children worldwide.”

For a field increasingly capable of protecting children before their first exposure to a pathogen, the next challenge may be less about whether the tools exist and more about whether health systems can deliver them equitably, consistently and with public trust.

For Prof. Esposito, prevention must ultimately be designed around “real children and real health systems. The future of infant immunization may depend on keeping both firmly at the center of innovation,” she concludes.