Current Advances in Tackling Respiratory Syncytial Virus

Medical News: Respiratory syncytial virus (RSV) is a significant cause of respiratory infections, particularly in vulnerable populations like infants, the elderly, and immunocompromised individuals. It leads to about 33 million lower respiratory tract infections annually in children under five, resulting in over 100,000 deaths globally. Similarly, among adults over 65, RSV contributes to severe pneumonia, chronic obstructive pulmonary disease exacerbations, and significant mortality rates, causing approximately 14,000 deaths annually. Despite decades of research, effective prevention and treatment methods for RSV have remained elusive, making the development of vaccines and therapeutic agents a global health priority.


Current Advances in Tackling Respiratory Syncytial Virus

Researchers from the Institute of Medical Biology, Chinese Academy of Medical Sciences, and Peking Union Medical College, along with international partners, are making strides toward addressing these challenges. This Medical News report delves into their study review findings and ongoing efforts to combat RSV through innovative vaccines and therapeutic strategies.
 
Breakthroughs in RSV Vaccines
For decades, RSV vaccine development faced setbacks, including safety concerns like enhanced respiratory disease (ERD) caused by early inactivated vaccines. However, recent advancements in structural biology have enabled the development of three vaccines: Arexvy, Abrysvo, and mRESVIA.
 
-Arexvy
Developed by GlaxoSmithKline (GSK), Arexvy was the first RSV vaccine approved by the US Food and Drug Administration (FDA) for adults aged 60 and older. It contains a stabilized version of the RSV F protein in its prefusion form, combined with the AS01E adjuvant to enhance immune responses. Clinical trials demonstrated an 82.6% efficacy against RSV-associated lower respiratory tract disease (LRTD) in its first season and 67.2% efficacy over two seasons, showcasing its potential for long-term protection.
 
-Abrysvo
Pfizer's Abrysvo, a bivalent vaccine targeting both RSV subtypes A and B, is adjuvant-free. It is approved for use in older adults and pregnant women. Trials showed a vaccine efficacy of 85.7% for LRTD with three or more symptoms in older adults. Administered during weeks 32 - 36 of pregnancy, it transfers protective antibodies to infants, reducing severe RSV disease by over 70% within the first six months postpartum.
 
-mRESVIA
Moderna’s mRESVIA is the world’s first mRNA-based RSV vaccine. Utilizing lipid nanoparticle delivery systems, it demonstrated an efficacy of 83.7% against severe RSV-LRTD in adults. However, its efficacy declined significantly after 18 months, emphasizing the need for booster doses to maintain protection.
(We at Thailand Medical News strongly recommends against using this vaccine)
 
Maternal Immunization for Infant Protection
Maternal vaccination represents a transformative approach to preve nting RSV in newborns. By vaccinating pregnant women, protective antibodies are passed through the placenta and breast milk. This method extends immunity to infants during their most vulnerable early months. Abrysvo’s approval for maternal immunization has been a significant milestone. However, trials observed a slight increase in preterm births among vaccinated mothers, prompting ongoing safety assessments.
 
Addressing Pediatric RSV
Developing vaccines for infants aged six months to five years remains a complex challenge. The risk of ERD and the immature immune systems of young children complicate vaccine design. However, live-attenuated and viral vector vaccines, which mimic natural infection and induce a broad immune response, are showing promise.
 
-RSVt Vaccine
Sanofi and the National Institute of Allergy and Infectious Diseases (NIAID) are developing the RSVt vaccine, which utilizes reverse genetic techniques to attenuate the virus. In Phase 1 trials, two doses elicited an immune response in 93% of infants, leading to Phase 3 trials involving over 6,000 participants.
 
-MV-012-968 and CodaVax-RSV
Meissa Vaccines’ MV-012-968 and Codagenix’s CodaVax-RSV are intranasal vaccine candidates designed to induce robust mucosal immunity. Both candidates have shown promising safety and efficacy profiles in early-stage trials, targeting the younger pediatric population.
 
Passive Immunization with Monoclonal Antibodies
Monoclonal antibodies (mAbs) offer an alternative approach for RSV prevention, particularly in high-risk groups like infants. Unlike vaccines, mAbs provide immediate protection by delivering preformed antibodies.
 
-Palivizumab (Synagis)
Palivizumab was the first mAb approved for RSV prevention in high-risk infants. However, its short half-life requires monthly injections, limiting its practicality and increasing costs.
 
-Nirsevimab (Beyfortus)
Nirsevimab, developed by AstraZeneca and Sanofi, has revolutionized passive immunization. With a prolonged half-life of over 100 days, a single dose provides season-long protection. Approved in Europe, it targets site Ø on the RSV F protein, offering over 50 times greater neutralizing activity than palivizumab.
 
However, there are many emerging concerns about the usage of this monoclonal drug.
https://www.thailandmedical.news/news/french-researcher-warns-against-beyfortus-nirsevimab-use-for-rsv-in-children
 
Challenges in Long-Term Immunity
One of the most pressing issues in RSV prevention is the waning immunity observed with current vaccines and antibodies. For instance, while Arexvy and Abrysvo demonstrated strong protection in their first season, their efficacy dropped significantly by the second season. Similarly, mRESVIA’s protection against severe disease declined to about 50% after 18 months. These findings indicate the potential need for periodic boosters, complicating widespread vaccine implementation.
 
Exploring Multivalent and Combination Vaccines
RSV’s antigenic variability across subtypes and seasons has driven the development of multivalent vaccines targeting multiple strains. Combination vaccines that include RSV, influenza, and COVID-19 antigens are also under investigation. Moderna’s mRNA-1230, for instance, combines antigens for RSV, influenza, and SARS-CoV-2, offering the possibility of “one-shot” respiratory protection.
 
Safety Concerns and Unresolved Questions
Despite these advancements, unresolved safety concerns persist. The association between RSV vaccines and conditions like Guillain-Barré Syndrome in older adults and preterm births in maternal immunization trials underscores the need for vigilant post-marketing surveillance. Additionally, challenges such as defining surrogate endpoints for vaccine efficacy, optimizing animal models for preclinical testing, and addressing the high costs of monoclonal antibody production require further research.
 
Conclusion
The fight against RSV has reached pivotal milestones with the approval of innovative vaccines and monoclonal antibodies. These tools are already making a difference in protecting high-risk groups, but challenges remain in expanding access, addressing safety concerns, and ensuring long-term immunity. With ongoing advancements in structural biology, genetic engineering, and vaccine design, the global health community is poised to overcome these hurdles, ultimately reducing the burden of RSV worldwide.
 
The study review findings were published in the peer-reviewed journal: MedComm.
https://onlinelibrary.wiley.com/doi/10.1002/mco2.70016
 
For the latest RSV News, keep on logging to Thailand Medical News.
 
Read Also:
https://www.thailandmedical.news/news/herbal-extracts-that-can-inhibit-respiratory-syncytial-virus-rsv-replication
 
https://www.thailandmedical.news/news/how-rsv-dodges-our-body-s-defense