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Immunodeficiency and Autoimmune Disorders / Respiratory Viral Infections Research · Journal article
The Journal of Immunology · July 28, 2026
Encouraging direction, but not yet definitive.
This controlled human infection model in older adults reveals preserved serum neutralising antibody responses but altered mucosal immunity with age, and identifies G-specific nasal IgA as a potential correlate of protection. The finding is mechanistically interesting but exploratory; G-specific IgA targeting is not a feature of current approved RSV vaccines, so clinical implications remain speculative pending larger studies and vaccine trials.
Prospective controlled human infection model with age-stratified comparison. Healthy older adults (60–75 years) and young adults (18–55 years); setting and detailed eligibility criteria not specified in abstract.. Intervention: Intranasal inoculation with RSV A Memphis-37. Compared with: Age-stratified comparison (older vs young); analysis also included historical samples from young adults in a previous CHIM using the same virus. n = 36.
Older adults showed higher infection rates (68% vs 31%) and greater viral shedding than young adults Pre-existing serum neutralising titres correlated with protection in older adults but not young adults G-specific nasal IgA in older infected adults correlated with protection from infection
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These findings suggest that current RSV vaccines targeting only pre-F protein may not optimally engage the mucosal immune responses that appear relevant to protection in older adults. The G-specific nasal IgA correlate warrants investigation in future vaccine designs, though confirmation in larger and vaccine-trial populations is essential before clinical recommendations change.
A controlled human infection model in older adults identifying age-related immune correlates of RSV protection, but a small single-centre study with exploratory endpoints that requires confirmation in vaccine trials.
As stated by the source record.
Quoted from the source exactly as published.
These findings suggest that current RSV vaccines targeting only pre-F protein may not optimally engage the mucosal immune responses that appear relevant to protection in older adults. The G-specific nasal IgA correlate warrants investigation in future vaccine designs, though confirmation in larger and vaccine-trial populations is essential before clinical recommendations change.
Graded across the dimensions that decide whether you should act, each from what the source actually supports. There is no single score, and where a dimension was not assessed it says so.
Abstract Introduction Respiratory syncytial virus (RSV) is a major cause of respiratory viral illness in older adults, yet the effect of ageing on systemic and mucosal immunity against RSV infection remain unclear. Using a RSV controlled human infection model (CHIM) in young and older adults, we examined early humoral and mucosal immunity, identified age-related immune differences, and explored immune correlates of protection at both systemic and airway sites. Methods Twenty-eight older (60—75 years) and 8 young (18—55 years) adults were inoculated intranasally with RSV A Memphis-37. Viral loads were measured by qPCR. Symptoms and paired serum, nasal, and bronchoalveolar lavages (BAL) were collected longitudinally. Neutralising antibodies and F and G protein—specific responses were quantified. Samples from a previous young adult CHIM using the same virus were also included. Results Older adults showed higher infection rates (68% vs 31%) and greater viral shedding. Pre-existing serum neutralising titres correlated with protection in older, but not young adults. Serum IgG responses were comparable across age groups and targeted pre-F epitopes. Nasal IgA responses while intact overall, showed limited boosting of pre-F-specific antibodies, that have the most potent neutralising activity. Multiplex analysis confirmed these patterns and demonstrated increased G-specific nasal IgA in older infected adults, which was correlated with protection. A similar pattern was also seen in BAL samples, but these did not correlate with protection from infection. Conclusion RSV CHIM in older adults is safe and reveals preserved systemic neutralising and IgG responses. Healthy older adults, however, were more susceptible to infection and exhibited distinct mucosal antibody profiles, with G-specific nasal IgA emerging as a potentially strong correlate of protection. These findings have implications for vaccine design in older adults, particularly as current approved vaccines only target RSV pre-F protein. Funding Source National Institute of Health Research; United Kingdom Research and Innovation Topic Categories Viral Immunology (VIR)
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