Respiratory syncytial virus (RSV) infection, especially in the elderly and older adults with one or more comorbidities, may lead to severe complications that require hospitalization, or even death. At the 2nd Hong Kong RSV Summit, Professor Ivan Hung of the Department of Medicine, University of Hong Kong, Hong Kong, and Professor Lucy Morgan of the University of Sydney and Macquarie University, Sydney, Australia, discussed efficacy and safety data of the recombinant adjuvanted RSVPreF3 vaccine and the importance of protecting the high-risk population ≥50 years of age against RSV infection and infection-associated risks.
High burden of RSV infection
“A global study found that in adults hospitalized with acute respiratory tract infections, rates of complications and mortality resulting from RSV are similar to those reported with influenza infections [lower respiratory complications (52.5 vs 49.7 percent), bacterial superinfection (36.6 vs 38.6 percent), cardiac complications (31.7 vs 24.1 percent), hospital readmission within 3 months postdischarge (26.9 vs 20.4 percent), deaths during hospitalization (2.5 vs 1.6 percent],” said Morgan. “These postinfection sequelae impose significant costs on both the individual and the community.” [Open Forum Infect Dis 2021;8:ofab491]
“Consistent with the rest of the world, the annual disease burden of RSV infection in Hong Kong is comparable with that of seasonal influenza,” reported Hung. “A retrospective study by the Chinese University of Hong Kong found that 30-day and 60-day crude all-cause mortality rates for RSV-infected patients [mean age, 75 years; with underlying conditions, 87 percent] in 2009–2011 were 9.1 and 11.9 percent, respectively, and the mean length of hospital stay of survivors was 12 days.” [Clin Inf Dis 2013;57:1769-1077]
The economic burden of RSV in older adults from direct medical costs was about HKD 591 million in 2022, with lower respiratory tract disease (LRTD) accounting for 97.6 percent of the costs. [Yufan Ho, et al, APSR 2024, abstract AO10-005.] “Hence, a better surveillance system under the Hospital Authority and Centre of Health Protection [CHP] on RSV disease, prevention and especially RSV-related LRTD and complications is needed,” suggested Hung.
Exacerbation of underlying diseases
According to a US study, among patients ≥60 years old who experienced exacerbation of comorbidities during RSV-associated hospitalization, 80 percent had chronic obstructive pulmonary disease (COPD), 50 percent had asthma, and 38 percent had congestive heart failure (CHF) as underlying chronic illness. [J Infect Dis 2020;222:1298-1310]
“RSV is associated with exacerbation of underlying disease [such as cardiovascular disease (CVD), including CHF and ischaemic heart disease, COPD, asthma, and diabetes], resulting in a very high risk of mortality. Even if patients survive the events, functional status deterioration is observed after recovery from the RSV infection,” highlighted Hung. [J Infect Dis 2020;222:1298-1310; Influenza Other Respir Viruses 2022;16:1151‐1160]
Who are at high risk of RSV infection and severe disease?
“Age, long-term care facility residence, and cardiopulmonary conditions are associated with severe RSV-related disease,” said Hung. [MMWR Morb Mortal Wkly Rep 2023;72:1075-1082]
“The older [≥50 years] we get, the more at risk we are of catching RSV and succumbing to severe RSV-associated complications, hospitalization and death. Canadian data showed that although the ≥65-year-olds make up only about 20 percent of RSV-attributed hospitalizations, these older patients make up a disproportionate percentage [85 percent] of those who die during hospitalization, compared to the 5–64-year-olds [12 percent],” said Morgan. [Influenza Other Respir Viruses 2022;16;1072-1081]
“Comorbidity is a major driver of complications, hospitalizations and death, although age itself or immunosenescence and weakened immune systems [whatever the cause] are likely driving factors for the increased risk of RSV infection in the first place,” she noted. [www.cdc.gov/rsv/high-risk/ older-adults.html; Open Forum Infect Dis 2018;27;5:ofy316; Clin Infect Dis 2022;74:1004-1011; Adv Ther 2020;37:1203-1217]
In Hong Kong, CHP’s 2016– 2024 surveillance data (excluding the COVID-19 period in 2020–2022) showed that >90 percent of fatal cases among public hospital patients during an RSV infection–associated hospitalization episode involved persons aged ≥65 years. [Communicable Diseases Watch 2025;21:1]
Adjuvanted RSVPreF3 vaccine
“RSV F protein–specific T-cell responses have been found to be deficient in older adults compared with younger individuals,” said Morgan. [Clin Vaccine Immunol 2013;20:239- 247; J Clin Dis 2023;227:761-772]
“As immunity wanes with age, the declining T-cell response makes it challenging for older adults not only to mount an immune response to RSV, but also to achieve and maintain higher levels of protection with vaccination. This has been a factor limiting the efficacy of RSV vaccinations to date,” she explained. [Vaccines (Basel) 2021;9:624; Clin Vaccine Immunol 2013;20:239-247]
Inducing high and persistent immune response with good safety profile
“The adjuvanted RSVPreF3 vaccine, where the RSVPreF3 antigen is combined with the AS01E adjuvant system, is able not only to restore that T-cell response, but also to boost it up and improve the quality and quantity of immune cells that have been waning,” highlighted Morgan. “The AS01E adjuvant system can boost cellular immune response and restore RSVPreF3 CD4+ T-cell level in older adults, as well as generate a higher and more persistent immune response.” (Figure) [Curr Opin Immunol 2015;35:30-38; J Infect Dis 2023;227:761-772; Expert Rev Vaccines 2018;17:619-634; Semin Immunol 2018;39:14-21; Signal Transduct Target Ther 2023;8:283]
A single dose of the recombinant adjuvanted RSVpreF3 vaccine has demonstrated high efficacy in the ongoing phase III AReSVi-006 trial across 17 countries spanning the Northern and Southern hemispheres, which included 24,967 participants aged ≥60 years (with coexisting chronic respiratory/pulmonary disease, CHF, cardiorespiratory disease, type 1 or 2 diabetes, advanced liver or renal disease, 40 percent). [N Engl J Med 2023;388:595-608] Vaccine efficacy rates against severe RSV-related LRTD were 94.1 percent during season 1 (first year; 6.7 months), 82.7 percent through season 2 (17.7 months), and 72.3 percent in season 3 (30.6 months). Protection in the first year against RSV-related LRTD was 94.6 percent in patients with ≥1 comorbidity of interest and 100 percent in those with ≥1 endocrine metabolic condition. The vaccine also protected against both RSV-A and RSV-B subtypes, with 84.6 and 80.9 percent efficacy rates, respectively, in the first year. [N Engl J Med 2023;388:595- 608; Clin Infect Dis 2024;78:1732- 1744; CHEST 2024, poster 3391; Clin Infect Dis 2024;78:202-209]
“Not many therapies in my prescription pocket can offer this kind of protection, particularly for patients with such significant comorbidities,” noted Morgan. “The adjuvanted RSVPreF3 vaccine has demonstrated the longest duration of protection among RSV vaccines – for at least three RSV seasons [30.6 months]. It is well tolerated, with no cases of Guillain-Barre Syndrome or acute disseminated encephalomyelitis reported over 31.7 months of safety follow-up.” [CHEST 2024, poster 3391; Lancet Respir Med 2025;doi:10.1016/S2213-2600(25)00048-7]
In adults aged 50–59 years with or without associated comorbidities, humoral response to adjuvanted RSVPreF3 vaccine is noninferior to that in ≥60-year-olds, with a consistent safety profile. [Clin Infect Dis 2024;79:1074-1084]
Latest recommendations
The US Centers for Disease Control and Prevention (CDC) Advisory Committee on Immunization Practices (ACIP) recommends a single dose of RSV vaccine in all adults aged ≥75 years. In April 2025, the recommendation expanded to those aged 50–74 years (previously 60–74 years) with certain chronic medical conditions or other factors that increase the risk of severe RSV disease. [MMWR Morb Mortal Wkly Rep 2024;73:696- 702; www.cdc.gov/acip/downloads/ slides-2025-04-15-16/06-Melgar-Surie- adult-rsv-508.pdf]
“It is worth noting that the 2025 update of the Global Strategy for Asthma Management and Prevention by the Global Initiative for Asthma [GINA] advises vaccination against RSV [amongst others] in adults and the elderly with asthma, and mentions the use of adjuvanted RSV-subunit vaccine in reducing upper and lower respiratory tract disease in adults ≥60 years old,” said Morgan. [www.ginasthma.org]
“In Hong Kong, the adjuvanted RSVPreF3 vaccine is the only adjuvanted recombinant RSV vaccine currently available. It is also the only RSV vaccine indicated for active immunization and prevention of LRTD caused by RSV infection in adults 50–59 years of age who are at increased risk of RSV disease [eg, chronic pulmonary disease, chronic CVD, diabetes, chronic kidney or liver disease] – an indication newly approved in Hong Kong – as well as all adults ≥60 years old,” she noted. [Arexvy Hong Kong Full Prescribing Information (HK67997)]
“Elderly persons [especially those aged ≥75 years, or those living in residential care homes] may consider RSV vaccination for personal protection, as an individual decision under informed consent in consultation with their doctors, as recommended by CHP’s Scientific Committee on Vaccine Preventable Diseases recently,” said Hung. [https://www.chp.gov.hk/files/pdf/interim_ consensus_on_the_use_of_respiratory_syncytial_virus_vaccines_in_ hong_kong_jan2025.pdf]