Vaccination for Respiratory Syncytial Virus: A Narrative Review and Primer for Clinicians

Respiratory syncytial virus (RSV) poses a significant burden on public health, causing lower respiratory tract infections in infants, young children, older adults, and immunocompromised individuals. Recent development and licensure of effective RSV vaccines provide a promising approach to lessening the associated morbidity and mortality of severe infections. This narrative review aims to empower clinicians with the necessary knowledge to make informed decisions regarding RSV vaccination, focusing on the prevention and control of RSV infections, especially among vulnerable populations. The paper explores the available RSV vaccines and existing evidence regarding their efficacy and safety in diverse populations. Synthesizing this information for clinicians can help the latter understand the benefits and considerations associated with RSV vaccination, contributing to improved patient care and public health outcomes.


Introduction
Respiratory syncytial virus (RSV) was first called chimpanzee coryza agent in 1956, following its discovery during an outbreak investigation into a group of chimpanzees with cold-like symptoms [1].It was then renamed as RSV after being isolated from human infants with acute respiratory disease [2,3].Since Beem's seminal 1960 report on RSV in children [4], RSV is now known to affect humans of all ages.RSV is the leading cause of severe lower respiratory tract disease (including pneumonia), hospitalizations, and fatalities among infants and young children [5].Among adults (particularly in individuals aged 65 and above), RSV is one of the main causes of community-acquired pneumonia and is a major contributor to morbidity, mortality [6], rehospitalization [7], and reduced quality of life [8].
RSV is an enveloped RNA virus belonging to the Pneumoviridae family and is classified into two subtypes, A and B [9].It consists of a nucleocapsid protein complex, a matrix protein layer, and three transmembrane glycoproteins.The fusion protein (F) and attachment glycoproteins (G) play crucial roles in viral entry and membrane fusion.RSV F is initially synthesized as an inactive precursor (F0) that undergoes cleavage to form fusioncompetent subunits (F1 and F2).The fusion process involves conformational changes in the prefusion state of RSV F (i.e., preF), leading to the insertion of the fusion peptide into the target membrane and the formation of a six-helix bundle that facilitates membrane fusion.Currently available vaccines [10,11] target the highly conserved preF and aim to generate neutralizing antibodies against it.
RSV infections commonly result in seasonal outbreaks worldwide [12].In the northern hemisphere, these outbreaks typically happen between October to May.Conversely, in the southern hemisphere, outbreaks usually occur from May to September.In tropical and semitropical regions, seasonal outbreaks of RSV are less distinct compared to temperate regions and are often associated with the rainy seasons and humid conditions [13,14].
Nearly all children experience RSV infection by two years of age, and reinfections are frequent.RSV is the main cause of lower respiratory infections in children [5], which, in turn, is the second most common cause of mortality in children younger than five years in 2019 [15].Globally, RSV is responsible for one out of every 50 deaths in children aged 0-60 months and one out of every 28 deaths in children aged 28 days to 6 months [5].Similarly, RSV can cause morbidity and mortality in adults.A systematic review of 103 studies published between 2000 and 2019 in developed countries evaluated the disease burden and healthcare utilization associated with RSV in older adults (aged ≥ 60 years) and high-risk individuals with comorbidities.The study found that RSV accounted for 4.7-7.8% of symptomatic respiratory infections in older adults, with a case fatality proportion of 8.2%.Among high-risk adults, RSV caused about 7.0-7.7% of symptomatic respiratory infections, with a case fatality proportion of 9.9% [16].
The healthcare impact of RSV infection rivals that of influenza in older adults, with a systematic review demonstrating comparable rates of hospitalization and mortality [17].For instance, among hospitalized patients in the United States, RSV and influenza A resulted in comparable hospital stays, intensive care unit admission (15% and 12%, respectively), and mortality rates (8% and 7%, respectively) [18].Notably, RSV infections were responsible for 11.4% of chronic obstructive pulmonary disease hospitalizations, 10.6% of pneumonia hospitalizations, 7.2% of asthma hospitalizations, and 5.4% of congestive heart failure hospitalizations [18].More recent studies even suggest that RSV causes more severe disease than influenza, with greater rates of mechanical ventilation, intensive care unit admission, and mortality [19,20].
Further data highlight the substantial economic burden of RSV hospitalizations among older adults.According to a study conducted in Ontario, Canada, there were 7091 adults hospitalized with RSV between 2010 and 2019 [21].The study found that the difference in healthcare costs between RSV-admitted patients and matched controls grew from $28,260 in the first 6 months to $43,721 at 2 years post-hospitalization.
Although RSV is important to individual and population health, even healthcare workers may have poor knowledge about RSV and RSV vaccination [22].This narrative review, therefore, aims to serve as a practical primer for clinicians who are unfamiliar with RSV vaccination and will focus on two broad questions: What is the clinical course, investigation, and treatment of RSV infection?2.
What are the relevant clinical studies and guideline recommendations supporting RSV vaccination?
With an improved understanding of both RSV infection and RSV vaccination, clinicians can then better guide patients regarding RSV vaccination.

Methods
PubMed ® (pubmed.ncbi.nlm.nih.gov) was used to search the MEDLINE database for contemporary literature over the past 3 years (from 1 October 2020 to 21 October 2023) and to update the author's personal library of articles.The search terms were "(respiratory syncytial virus) AND (vaccination OR vaccine*)".Titles and abstracts were screened to look for relevant articles that provided new insights for the narrative review.

Results of the Literature Search
The search yielded 1164 articles, and 72 articles were included.Another 23 articles were used from the author's personal library of articles.As such, 95 articles were included in this narrative review.

Clinical Course of RSV Infection
RSV commonly attacks the bronchopulmonary epithelium, causing lower respiratory tract disease, airway inflammation, sputum production, and bronchospasm.Symptoms include fever, cough, breathlessness, and wheezing [23].These symptoms are non-specific and can occur with other viral respiratory infections.Symptoms peak in severity 5-7 days after illness onset.Within the first two weeks of infection, RSV can be recovered from the nasopharynx [24].
Extrapulmonary RSV infection can occur in both immunocompetent and immunocompromised patients, e.g., otitis media [25], encephalitis [26], and myocarditis [27].In children aged < 15 years old, RSV is responsible for up to 6.5% of acute encephalitis, with 85% of cases presenting with seizure [26].Other RSV-associated complications have also been reported in severely ill children who require mechanical ventilation, with elevated cardiac troponin levels in up to 54%, raised hepatic transaminases in up to 49%, and hyponatremia in about 33% [28].
Patients at risk for severe RSV lower respiratory tract disease are those with impaired immunity or reduced cardiorespiratory reserve.These patients include immunocompromised patients (e.g., solid organ transplant and hematopoietic stem cell transplant patients) [29,30], patients 65 years or older [31]), and patients with the following list of chronic conditions [32][33][34]:

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Active or past tobacco smoking Functional recovery after RSV infection may be incomplete.As an example, 39% of RSV-infected individuals residing in homeless shelters indicated that their ability to carry out their usual activities was significantly affected by their illnesses [35].Separately, the protective humoral antibody response after natural RSV infection is short-lived; reinfection is possible in most people two months or more after natural infection [36].

Investigation of RSV Infection
As observed in chest computed tomography scans, the radiographic manifestations of RSV infection can encompass a range of features, such as localized or widespread interstitial or ground-glass pulmonary opacities, thickening of bronchial walls, tree-in-bud patterns, and lobar consolidation [37].These findings lack specificity and may resemble those seen in influenza and parainfluenza viral infections, although it is worth noting that RSV infection tends to localize in the upper and middle lobes of the lung [37].
Given nonspecific clinical and radiographic findings of RSV infection, definitive diagnosis requires demonstration of live virus in culture, viral components (RSV antigen), positive acute viral serology, or viral RNA.Although viral culture is considered the gold standard, it is not feasible for clinical settings due to its extended turnaround time of up to one week and its limited sensitivity.Molecular methods are preferred, given high sensitivity, high specificity, and rapid turnaround times within hours [38].Such molecular assays may even be available as point-of-care tests, which provide both convenience and timeliness for clinicians and patients [39].Respiratory sampling for RSV is most easily carried out using nasopharyngeal or mid-turbinate nasal swabs.RSV samples can also be obtained from oropharyngeal swabs or from bronchoalveolar lavage.
According to a systematic review and meta-analysis of studies conducted between January 2000 and December 2021, singleplex reverse transcription polymerase chain reaction (RT-PCR) is the most sensitive diagnostic method for RSV in adults [40].Using singleplex PCR as the reference standard (i.e., assumed sensitivity of 100%), other methods, such as rapid antigen detection test, direct fluorescent antibody, viral culture, and multiplex PCR, were less sensitive (pooled sensitivity 64%, 83%, 86%, 93%, respectively).The addition of various specimen types to nasopharyngeal swab RT-PCR testing significantly increased RSV detection rates, e.g., sputum RT-PCR increases detection by 1.5 times, and oropharyngeal RT-PCR increases detection by 1.3 times.Testing multiple specimens is, therefore, a useful strategy when the clinical suspicion for RSV infection is high but the initial nasopharyngeal PCR test is negative.

Treatment of RSV Infection
Supportive therapy is the primary approach for managing lower respiratory tract infection caused by RSV as specific antiviral therapy is not generally available.Ribavirin, a nucleoside analog, demonstrates good activity against RSV in laboratory settings [41].Oral ribavirin has, however, not shown clinical benefits, while the aerosolized form (2 g over 3 h every 8 h, for 5-10 days [42]) has been considered for off-label use to prevent the progression of RSV upper respiratory tract infection to lower respiratory tract disease in immunocompromised individuals, e.g., hematopoietic stem cell transplant recipients [29,30].
EDP-938, an orally administered, small-molecule, non-fusion replication inhibitor targeting RSV nucleoprotein, holds significant potential as a treatment option.In a doubleblind, randomized, placebo-controlled human virus challenge trial, it demonstrated superiority over a placebo in terms of reducing viral load, total symptom scores, and mucus weight while showing no apparent safety issues [43].
A novel nebulized trivalent nanobody (ALX-0171) with antiviral properties against RSV was studied in a double-blind, randomized, placebo-controlled, phase 2b trial in 50 hospital pediatric departments across 16 countries.However, despite decreasing viral load, ALX-0171 failed to improve oxygenation or disease severity in hospitalized children with RSV-related lower respiratory tract infection [44].

General Principles for Prevention of RSV Infection
Given the dearth of specific treatment options, especially after lower respiratory tract disease develops, prevention rather than treatment remains key to decreasing the health burden of RSV.As RSV is primarily transmitted by nasopharyngeal spread and ocular/mucous membrane inoculation, prevention of infection can be carried out by masking, cough hygiene, hand washing, and avoiding close contact with infected persons.Nosocomial transmission of RSV should be prevented via strict infection control, as outcomes of healthcare-associated RSV infection may be worse than in community-acquired infections.For instance, in a population-based, surveillance study of RSV-infected hospitalized adults, healthcare-associated infections required a higher level of care at discharge (i.e., placement in a skilled nursing or rehabilitation facility) compared with community-acquired infections (44% vs. 14%) [45].
Direct infant immunization is currently not available.Concerns exist over vaccineenhanced RSV disease in patients without prior RSV infection [46], and proposed mechanisms encompass several pathways [47].Firstly, antibody-dependent enhancement (ADE) involves vaccine-generated antibodies that fail to neutralize the virus.Secondly, immune complex accumulation and deposition in the lungs trigger an inflammatory environment, antibody production, and complement cascade activation, potentially worsening the disease.Thirdly, skewing the immune response toward a Th2 phenotype results in pulmonary eosinophil infiltration and disease exacerbation.Nonetheless, recent clinical trials in RSVseronegative infants and children seem to suggest that vaccine-enhanced RSV disease may not always occur [48,49].
Until pediatric RSV vaccination is available, prevention of RSV disease in infants and children requires either immunoprophylaxis with monoclonal antibodies or transplacental transfer of maternal RSV antibodies following maternal vaccination during pregnancy.Palivizumab (Synagis TM , AstraZeneca/MedImmune) is a humanized monoclonal antibody that targets the RSV F glycoprotein [50].Palivizumab is given via monthly intramuscular injections during the RSV season to protect children from severe lower respiratory tract infections caused by RSV [51].Nirsevimab (Beyfortus TM , AstraZeneca/Sanofi) is another monoclonal antibody for RSV immunoprophylaxis that targets the prefusion conformation of the RSV F glycoprotein [52].Nirsevimab possesses a prolonged half-life, and a single injection appears to be effective.Compared to the multiple monthly injections required for palivizumab, the single-dose regimen for nirsevimab makes it a more convenient monoclonal antibody option.Immunoprophylaxis with monoclonal antibodies is costeffective in both high-income [53] and resource-limited countries [54,55].

Vaccination for Prevention of RSV Infection
To prevent RSV-associated lower respiratory tract infections in infants born during their first RSV season or entering it, administering maternal RSVpreF vaccination between 24 and 36 weeks of gestation during pregnancy is an alternative to providing immunoprophylaxis.Only one vaccine (Abrysvo TM , Pfizer Inc., New York, NY, USA) is available for this purpose [56], which contains stabilized preF from the two main RSV antigenic subgroups A and B. The RSV vaccine stimulates maternal production of protective antibodies against RSV, which takes about two weeks.Transplacental transfer of these antibodies then protects newborns and infants from severe RSV infection [57].
In the pivotal Phase 3 trial by Kampmann et al. [57], which recruited pregnant women between 24 and 36 weeks of gestation, numerically more cases of preterm births occurred in vaccinated compared to unvaccinated pregnant women (229 versus 198).Although the difference in the proportion of preterm births (6.4% versus 5.5%) was not statistically significant, to mitigate the risk of preterm births, the U.S. Food and Drug Authority approved maternal vaccination only for pregnant women between 32 and 36 weeks of gestation (Table 1).Similarly, both the American College of Obstetricians and Gynecologists and the U.S. Centers for Disease Control and Prevention limit their recommendations for maternal vaccination to 32-36 weeks of gestation (Table 2).Nonetheless, in contrast to the United States-based regulators, the European Medical Agency (EMA) licensed Abrysvo TM on 23 August 2023 for maternal vaccination women in weeks 24-36 of gestation [58].
After maternal RSVpreF vaccination, immunoprophylaxis for infants is generally not needed [59].However, special infant-related and maternal circumstances may necessitate immunoprophylaxis despite maternal RSVpreF vaccination [10].Firstly, infants who are born within the first 14 days after maternal RSVpreF vaccination since a minimum of 14 days is required after maternal vaccination for the development.Secondly, infants who lose maternal antibodies due to cardiopulmonary bypass or extracorporeal membrane oxygenation.Thirdly, infants with especially high risk for severe RSV disease and who require enhanced protection from RSV, such as those with hemodynamically significant congenital heart disease or those with ongoing respiratory failure at hospital discharge.Fourthly, mothers with immunocompromise and who do not mount an adequate immune response to vaccination.Fifthly, mothers living with human immunodeficiency virus infection who have reduced transplacental antibody transfer.
Pregnant individuals can receive the maternal RSVpreF vaccine concurrently with other recommended vaccines, including tetanus, diphtheria, and pertussis (Tdap), influenza, and COVID-19 vaccines.The timing of administration, including the option for simultaneous vaccination at different anatomic sites on the same day, is flexible and not restricted [10].Although RSVpreF and Tdap vaccines can be coadministered, the immunogenicity of the pertussis component may be blunted, though it seems to remain protective [60].
In contrast to infants, direct immunization of older adults is available, given that most adults would have been infected by RSV previously in their childhood or early adulthood.Two vaccines are currently available for adults aged 60 years and above: a non-adjuvanted bivalent vaccine (Abrysvo TM , Pfizer Inc., which is the same one used for maternal vaccination) and an adjuvanted non-bivalent vaccine (Arexvy TM , GSK Inc., London, UK) (Tables 1 and 2).

Evidence Supporting Efficacy and Safety of RSV Vaccination
This section provides the evidence that supports maternal RSV vaccination (for prevention of infection in infants) and RSV vaccination in older adults.The usual endpoint for clinical trials is the relative risk (RR) of developing symptomatic disease.Using data from a randomized clinical trial, the RR is calculated as the ratio of the probability of symptomatic disease in the vaccinated group to the probability of symptomatic disease in the unvaccinated group.Vaccine efficacy (VE) is then expressed as a percentage by subtracting the relative risk (RR) from 1 and then multiplying by 100, i.e., VE = (1 − RR) × 100%.
During the development of maternal RSV vaccination, RSVpreF vaccine candidates were first tested in healthy nonpregnant women to demonstrate immunogenicity (i.e., generation of serum-neutralizing responses) and safety (i.e., absence of major side effects or severe reactogenicity) [60,62,63] (Table 3).Then, trials of RSV vaccination in pregnant women [57,64,65] were conducted (Table 4).While developing the RSVpreF (non-adjuvanted, bivalent) vaccine (Abrysvo TM , Pfizer Inc.), studies found that pregnant women between 24 and 36 weeks of gestation appropriately developed neutralizing antibodies against both RSV-A and RSV-B following bivalent RSVpreF vaccination, but the humoral responses were not significantly different between lower (120 mcg) and higher (240 mcg) vaccine doses [64].Furthermore, using an aluminum hydroxide adjuvant in-creased postvaccination reactions (e.g., infections, gastrointestinal conditions) without improving immunogenicity.As such, the final formulation of bivalent RSVpreF vaccine for maternal vaccination uses the 120 mcg dose without adjuvant [57].
Like in maternal RSV vaccination, during the development of RSV vaccination for older adults, RSVpreF vaccine candidates were shown to be immunogenic and safe in healthy young and older adults [56,66] (Table 3).The same formulation of the non-adjuvanted, bivalent RSVpreF vaccine (Abrysvo TM , Pfizer Inc.) is used in pregnant women and older adults aged 60 years and above [32] (Table 4).For the non-bivalent RSVpreF3 vaccine (Arexvy TM , GSK Inc.), the 120 mcg-dose with AS01E adjuvant had optimal immunogenicity and reactogenicity [66] and was thus used in the subsequent landmark clinical trial [33].
RSVpreF vaccination in pregnant [57] and older adults [32,33] is safe, with only mild-tomoderate side effects, such as injection site pain, myalgia, headache, and nausea.Although these vaccine-related reactogenicity events occur more frequently than when placebo vaccination is given, they resolve quickly within 2 to 3 days of onset and are, therefore, of minor clinical significance [57].Nonetheless, continued vigilance for adverse events is required even for the approved vaccines.From the trial by Kampmann et al. [57], while RSVpreF vaccination had no direct adverse effects on infants after maternal vaccination, numerically more cases of preterm births occurred in vaccinated compared to unvaccinated pregnant women.This difference was not statistically significant.In addition, from the U.S. Centers for Disease Control and Prevention review of RSVpreF vaccination trials in older adults [11], rare cases of severe inflammatory neurological events (e.g., acute disseminated encephalomyelitis and Guillain-Barré syndrome) surfaced.Though concerning, these cases could not be definitively linked to RSV vaccination.
For pregnant women, coadministration of RSVpreF and a variety of other vaccines (seasonal inactivated influenza vaccine [67,68], Tdap vaccine [60]) is possible without major safety concerns.Although the immunogenicity of the pertussis component of Tdap may be blunted (the reason for this is unknown), it remains protective [60].For older adults, coadministration of RSVpreF and influenza vaccine is possible, with good immunogenicity preserved for both vaccines, though reactogenicity may be increased [11].Numerically, more cases of preterm births and hypertension/pre-eclampsia in vaccinated pregnant mothers but these were not statistically significant.Incidences of adverse events within one month after injection or after birth were similar between the vaccine and placebo groups, with 13.8% of women and 37.1% of infants in the vaccine group experiencing adverse events, compared to 13 During the first 90 days of life, the vaccine group showed a lower percentage of infants with RSV-associated, medically significant lower respiratory tract infections at 1.5%, compared to the placebo group at 2.4% (vaccine efficacy of 39.4%, lower bound of 97.52% confidence interval of −1.0%, which did not meet prespecified success criterion) Injection-site reactions at the local level were more frequent in women who received the vaccine compared to those who received the placebo (40.7% vs. 9.9%).However, the percentages of participants experiencing other adverse events were similar in both groups

Limitations of This Narrative Review
This review used primarily the MEDLINE database, which contains literature published predominantly in the English language and may, therefore, miss out studies published in other languages.In addition, the inclusion of studies is subjective, though the review is meant to summarize key information from the clinical perspective rather than to systematically review all literature.Finally, the efficacy and safety of RSV vaccination in special populations, such as immunocompromised patients, are extrapolated from available data in immunocompetent patients, and further studies are required.

Future Directions
The year 2023 was the breakthrough year for RSV vaccination, with the publication of three pivotal trials leading to the authorization of two vaccines for vaccination of pregnant women and adults aged ≥ 60 years [32,33,57], though more trials are needed to elucidate the protective effect of vaccination on severe RSV outcomes, such as respiratory failure, extrapulmonary complications, functional outcomes, quality of life, and mortality.RSV vaccination should be further studied in other patient groups at risk for severe RSV disease, e.g., younger adults and children with immunocompromise [29] and chronic cardiopulmonary disease [34].For these younger adults, candidate vaccines have already demonstrated immunogenicity and safety in healthy individuals [56,66] and in the general population [67], while efficacy data are being accrued [56].For children and infants, studies of vaccination in both RSV-seronegative and RSV-seropositive individuals are underway, with candidate vaccines showing immunogenicity and safety (Table 5).For immunocompromised persons of varying levels of immunocompromise, immunogenicity will be blunted to varying degrees [85], and dedicated vaccination studies will be needed to elucidate the appropriate vaccine dosing regimen (including dose and need for repeat vaccination).Given that RSV-associated acute respiratory infections affect about 3.4% of pregnant women, with increased odds of preterm delivery [86], it will also be important to know if adult vaccination of pregnant mothers can benefit pregnancy outcomes.
Multiple vaccine platforms are being developed for RSV vaccination and for various target groups [87].Virus-like particle-based vaccines [69], mRNA-based vaccines [70,71], G protein-based recombinant vaccines [72], Mycobacterium bovis BCG-based recombinant vaccines [73], adenovirus vector-based vaccines [74][75][76] (development has been halted by its manufacturer in March 2023 after portfolio review), and Modified Vaccinia Ankara (MVA) poxvirus-based recombinant vaccines [78] have been immunogenic and well-tolerated in early trials in healthy participants.Beyond the trials in healthy participants, although a large multinational trial of RSV fusion protein nanoparticle vaccine did not reach its desired efficacy outcome [80], other platforms involving adenovirus vector-based vaccines [81,82,84] and mRNA-based vaccines appear more promising.The ConquerRSV trial, examining Moderna's mRNA-based RSV vaccine (NCT05127434), enrolled over 37,000 participants 60 years of age and older and attained its primary efficacy endpoint of preventing symptomatic RSV-associated lower respiratory tract disease; results regarding the prevention of severe disease are anticipated [88].For vaccination to be considered a success, vaccines need to reach their intended recipients.This objective can be achieved through the implementation of various strategies, which may encompass the following actions:

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Including RSV vaccination in global guidelines, especially those focusing on at-risk patients with chronic diseases [92].

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Including RSV vaccination in national policies and vaccination schedules, which would require not only efficacy/safety data, but also cost-effectiveness/economic impact data [93].Special consideration should also be given to vaccination's association with reduced disease and consequent antimicrobial prescribing [94].

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Improving access and affordability, especially in low-income and middle-income countries (LMICs), where over 95% of cases of RSV-associated acute lower respiratory infections and more than 97% of RSV-related deaths across all age groups occurred in children aged five years or younger [5].

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Addressing vaccine hesitancy, which is "the delay in acceptance or refusal of vaccines despite availability of vaccination services", as defined by the World Health Organization's Strategic Advisory Group of Experts on Immunization (SAGE).
Vaccine hesitancy is influenced by complacency, convenience, and confidence [95].To overcome complacency (diminished perception of the risk associated with vaccinepreventable diseases), healthcare providers need to convince at-risk individuals about the severity of RSV disease.To overcome inconvenience, health systems need to make RSV vaccination affordable and easily available.Coadministration of RSV vaccines with influenza vaccine seems to be safe and may be a useful means to improve convenience.To overcome the lack of confidence, more clinical trial and surveillance data will be needed to demonstrate an improvement in key patient outcomes (e.g., survival and quality of life) and absence of excess risk for severe adverse events (e.g., preterm births [79], acute disseminated encephalomyelitis and Guillain-Barré syndrome [11]).Recent vaccine acceptance surveys for maternal RSV vaccination have highlighted the need for layperson education to build trust in healthcare providers, provide evidence on vaccine efficacy, and address safety concerns.In addition, vaccines should be provided at a reasonable cost to reduce financial burden [96].In line with the aim of this narrative review, healthcare providers also need to be educated on RSV vaccination to improve the former's awareness and support for routine vaccination [97,98].

Conclusions
This review underscores the significant impact of RSV on global health, particularly in infants, young children, and older adults.It highlights the importance of timely diagnosis, supportive care, potential antiviral treatments, and vaccination for reducing the health burden of RSV infection.Maternal vaccination for infant protection and vaccination in older adults are now available, with ongoing efforts to extend vaccination to younger at-risk populations and to seronegative children.For RSV vaccination to be implemented successfully, global guidelines and national policies need to recommend RSV vaccination, and health systems need to ensure the affordability and accessibility of RSV vaccines, especially in low-and middle-income countries.Finally, more trial data and post-marketing surveillance of RSV vaccines will help build confidence in the long-term efficacy and safety of RSV vaccination.

Table 1 .
Available types of RSV vaccines.

Table 2 .
Selected guideline recommendations for RSV vaccination.

Table 3 .
Selected randomized clinical trials of RSV vaccines in healthy non-pregnant adults only (≥18 years old).

Table 4 .
Selected randomized clinical trials of RSV vaccines not restricted to healthy nonpregnant adults (≥18 years old).

Table 5 .
Selected randomized clinical trials of RSV vaccines in children (<18 years old).