Abstract
The respiratory syncytial virus (RSV) is a major cause of acute lower respiratory tract infection in children and poses a significant risk to older adults. Developing a vaccine against RSV has been a priority, and the recently approved Arexvy vaccine has shown promise in preventing lower respiratory tract disease (LRTD) caused by RSV in individuals aged 60 years and older. This comprehensive review discusses the history of RSV, challenges in vaccine development, and the mechanism of action of Arexvy. The efficacy and safety of the vaccine are explored based on phase 3 clinical trial, demonstrating its effectiveness in preventing RSV-associated LRTD. The most common adverse reactions reported include injection site pain, fatigue, myalgia, headache, and arthralgia. Ongoing research focuses on the long-term effectiveness of Arexvy, including the need for booster doses and its impact on reducing RSV-associated hospitalizations. The potential of Arexvy to lessen the burden of RSV-related illnesses, particularly in vulnerable populations, is highlighted, emphasizing the importance of widespread immunization efforts and accessibility to this groundbreaking vaccine.
Introduction
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Notably, nearly all children under the age of 2 years will experience an RSV infection, with approximately half of them being infected twice within this timeframe (Glezen et al., 1986). The recognition of RSV as a potentially serious issue among older adults occurred much later, in the 1970s, coinciding with outbreaks of the virus in long-term care facilities (Hart, 1984; Sorvillo et al., 1984). Subsequent studies conducted on hospitalized adults have provided further evidence that RSV could be a significant contributor to illness in elderly individuals residing in the community (Falsey et al., 2005). RSV has been widely recognized as a prevalent pathogen, causing a significant burden of disease on children, the elderly, and high-risk adults worldwide (Barr et al., 2019; Shang et al., 2021).
Since its discovery, numerous studies and clinical trials have been conducted in an effort to develop a vaccine against this common respiratory pathogen. Despite persistent efforts to discover pharmaceutical treatments to enhance the disease's clinical progression and results, the most successful treatment approach still revolves around providing supportive care (Wright and Piedimonte, 2011). Researchers worldwide have dedicated substantial resources to understanding the virus's structure (Fedechkin et al., 2018; McLellan et al., 2013; Ogra, 2004), replication mechanisms (Chapman et al., 2007; Li et al., 2018), and immune response dynamics to inform the development of effective preventive measures (Fuller and Del Mar, 2006; Griffiths et al., 2017; Turner et al., 2014).
One key area of investigation has focused on identifying the most suitable antigen targets for vaccine development. RSV possesses multiple surface proteins, including the fusion (F) protein, attachment (G) protein, and small hydrophobic (SH) protein, among others, which have been explored as potential vaccine candidates. Various preclinical studies utilizing animal models, such as mice, cotton rats, and nonhuman primates, have evaluated the immunogenicity and protective efficacy of these antigens (Munoz et al., 2017; Tremblay et al., 2019).
In addition to traditional protein-based vaccines, other vaccine platforms, such as live attenuated vaccines, viral vectors, and nucleic acid-based vaccines (DNA and mRNA), have also been investigated. These platforms offer unique advantages in terms of immunogenicity, safety, and ease of production (Kruijsen et al., 2018; McClellan et al., 2013).
Clinical trials have played a crucial role in assessing the safety and efficacy of candidate RSV vaccines. Phase 1 trials primarily focus on evaluating vaccine safety and dosing regimens in healthy adult volunteers. Subsequently, phase 2 trials expand the study population to include a broader age range and evaluate vaccine immunogenicity and protective efficacy. Phase 3 trials, involving large-scale efficacy studies, are pivotal in determining the overall effectiveness of the vaccine in real-world conditions (Chu et al., 2017; Griffin et al., 2017).
Despite considerable research efforts, the development of an RSV vaccine has faced challenges. One major obstacle has been the phenomenon of vaccine-induced enhanced respiratory disease (ERD), which was observed in a previous trial of an experimental RSV vaccine. ERD occurs when vaccinated individuals experience more severe respiratory symptoms upon subsequent natural infection with RSV. Understanding the immune mechanisms underlying ERD and developing strategies to mitigate its occurrence have been critical goals in RSV vaccine development (Polack et al., 2016; Qiu et al., 2022).
After extensive research, on May 23, 2023, the US Food and Drug Administration (FDA) granted approval to Arexvy (RSV vaccine, adjuvanted) that has shown remarkable potential in the prevention of LRTD caused by RSV in individuals aged 60 years and older (Foley et al.).
Arexvy's approval was granted after a comprehensive phase 3 trial involving a randomized sample of adults aged 60 years and above. The trial involved 12,467 participants who received a single dose of the RSV prefusion F protein-based vaccine, whereas 12,499 participants were assigned a placebo. Throughout a median follow-up period of 6.7 months, the vaccine demonstrated a remarkable efficacy rate of 82.6% (with a 96.95% confidence interval: 57.9–94.1) against RSV-related LRTD (Venkatesan, 2023).
This significant milestone marks the first ever approval of an RSV vaccine for older adults worldwide (Foley et al.). However, in individuals aged >80 years, who face a higher risk of severe disease, the efficacy rate decreased to 34%. Although the FDA granted approval for the vaccine, the CDC has not endorsed its broad utilization, especially among individuals aged >65 years. This caution is based on inconclusive data, indicating potential uncertainties or concerns regarding its application in this specific age group. In this comprehensive review, we will delve into the features, utility, efficacy, safety, and current research surrounding Arexvy, providing a comprehensive understanding of its role in RSV prevention.
Utility of Arexvy
Arexvy is recommended for active immunization to prevent LRTD caused by RSV in adults aged 60 years and above. The administration of this vaccine should align with official guidelines.
Mechanism of action of Arexvy
Arexvy functions by utilizing a combination of a recombinant subunit prefusion RSV F glycoprotein antigen (RSVPreF3) and the AS01E adjuvant. When administered, the vaccine stimulates the immune system in adults to produce a response specifically targeting RSVpreF3. This immune response helps protect against LRTD caused by RSV (Clinical Trials Arena, 2023).
Dosage and administration
Dose
To administer a single dose of Arexvy, a 0.5 mL intramuscular injection is recommended (DailyMed, 2023).
Administration
After reconstitution, it is important to either administer Arexvy immediately or store it appropriately to maintain its stability. The reconstituted vaccine should be protected from light and stored in the refrigerator between 2°C and 8°C (36°F to 46°F), or it can be stored at room temperature up to 25°C (77°F). It is crucial to use the reconstituted vaccine within 4 h. If the vaccine is not used within this timeframe, it should be discarded (DailyMed, 2023).
Efficacy
The vaccine has undergone a phase 3 clinical trial, AReSVi-006 (adult RSV), which evaluated its efficacy in preventing LRTD caused by RSV in adults aged 60 years and older.
The trial, conducted in 17 countries across the Northern and Southern Hemispheres [9], included 24,960 participants who received a single dose of either Arexvy or a placebo. Participants were followed for up to 10 months, with a median follow-up of 6.7 months. The primary analysis focused on participants who did not report an RSV-confirmed acute respiratory illness (ARI) before day 15 after vaccination.
Immunocompromised individuals were excluded from the study, but participants with pre-existing stable chronic diseases such as diabetes, hypertension, or cardiac disease were allowed to participate if deemed medically stable by the investigator. The analyzed population had a median age of 69.0 years, with 51.7% women and a diverse range of racial and ethnic backgrounds. Approximately 39.3% of participants had at least one comorbidity, including cardiorespiratory conditions (19.7%) and endocrine/metabolic conditions (25.8%) at baseline.
Based on the trial findings, Arexvy has demonstrated efficacy in preventing RSV-associated LRTD in older adults. The vaccine's effectiveness persisted across multiple RSV seasons and even after annual revaccination. These results indicate the potential of a single dose of Arexvy, in combination with the adjuvant, to provide protection against RSV-related LRTD in this specific age group (GlaxoSmithKline, 2023).
Safety Profile
Nonclinical data from standard studies on repeated dose toxicity do not indicate any specific risk to humans (European Medicines Agency, 2023).
In individuals aged 60 years or older, regardless of the subtype of RSV and the presence of underlying coexisting conditions, the administration of a single dose of the RSVPreF3 OA vaccine demonstrated a satisfactory safety profile. Furthermore, this vaccine effectively protected against RSV-related acute respiratory infections, LRTDs, and severe RSV-related LRTDs (Papi et al., 2023).
Studies conducted on the unadjuvanted RSVPreF3 vaccine, including reproductive and developmental investigations, as well as a rabbit study on Arexvy, did not identify any adverse effects related to the vaccine concerning female fertility, pregnancy, or the development of embryos, fetuses, or offspring (European Medicines Agency, 2023).
Adverse effects: According to the results of clinical trial NCT04886596 (ClinicalTrials.gov, 2023), the adverse reactions that were most frequently reported (≥10% of participants) included injection-site pain (60.9%), fatigue (33.6%), myalgia (28.9%), headache (27.2%), and arthralgia (18.1%) (GlaxoSmithKline, 2023).
Current Research and Future Directions
Ongoing research aims to further elucidate the long-term effectiveness of Arexvy, including its duration of protection and potential need for booster doses. In addition, investigations are being conducted to explore the vaccine's impact on reducing RSV-associated hospitalizations and overall disease burden in various populations, such as preterm infants and older adults (Mejias et al., 2020; Treskova et al., 2021). Furthermore, studies are underway to assess the feasibility of incorporating Arexvy into routine immunization schedules.
Conclusion
Arexvy holds great promise as a revolutionary vaccine for preventing RSV infections. With its demonstrated efficacy, favorable safety profile, and ongoing research endeavors, this vaccine could significantly reduce the burden of RSV-related illnesses, particularly in vulnerable populations. As the scientific community continues to gather more data and refine our understanding of Arexvy, it is crucial to prioritize immunization efforts and ensure widespread access to this groundbreaking vaccine.
Footnotes
Acknowledgments
I express my sincere gratitude to our Principal Dr. A.P. Basavarajappa who offered me to acquire knowledge from this institution. I also convey my sincere thanks to the assistant professors and head of the department of pharmacy practice for their valuable advice, insightful comments, motivations, and encouragements contributed. Finally, we express our gratitude to all the doctors of the SS Institute of Medical Sciences and Research Centre for their support and guidance.
Author Disclosure Statement
The authors declare that there is no conflict of interest in the research study.
Funding Information
No funding was provided and the research was carried out entirely at the authors' expense.