Effective Respiratory Syncytial Virus vaccines in older adults—the long wait is over

For most clinicians when you mention respiratory syncytial virus (RSV) the immediate association is with bronchiolitis in the very young. Although there is no question that RSV does cause significant disease in the very young, data suggests that it causes double the number of hospitalisations and 20–30 times more deaths in those over 65 years of age.1 In low- and middle-income countries the impact of RSV is even greater. In adults, clinicians are very familiar with RSV causing pneumonia, exacerbations of asthma and chronic obstructive airways disease. However, as diagnostic testing for RSV has improved and research has been directed towards understanding its impact, it has become apparent that these 'obvious' sequalae are just the tip of the iceberg. RSV is also responsible increased heart failure,2 myocardial infarction and stroke,3 and less obvious outcomes like fractures from falls in confused and debilitated elderly patients. Recent data also suggests that RSV is one of the major drivers of pneumococcal disease in the community.4 Equally outcomes from hospitalization with RSV is the same or worse than with influenza.5 Perhaps the most profound argument for the need for prevention of RSV is the large proportion of vulnerable elderly people in whom infection leads to a permanent loss of both physical and cognitive capacity with an associated loss of independence,6 something observed in other severe viral infections.7 After decades of stalled development, we now have at least three highly efficacious and safe RSV vaccines for adults over 60 years of age.8-10 While slightly different approaches have been taken by the three companies, they are all based on generating antibodies to the pre-fusion configuration of the RSV fusion protein using either recombinant prefusion F-protein or mRNA coding for it. All studies recruited subjects 60 years and over, with a significant focus on trying to enrol patients with significant comorbidities and/or over 75 years of age. Given efficacy of season influenza vaccine is typically no more than 40%, the 1-year efficacy estimates of between 62% and 72% for the three vaccines for RSV-related respiratory tract infection is very encouraging.8-10 Although none of the studies were powered to analyse hospitalisations, each of the three studies used various definitions of more severe lower respiratory tract infection with estimates ranging from 67% to 94%.8-10 Direct comparison of the results of the three studies is not possible as they were not head to head studies, had slightly different end point definitions, were not all conducted at the same time and the confidence intervals remain quite large due to a relatively low number of events, particularly in subgroups of interest like those with multiple comorbidities or advanced age. There is significant interest in the likely duration of effect of the vaccines, however published results for one of the three vaccines suggests good protection exists for at least a second year.11 Interestingly in the same vaccine study, a subset of patients received a second dose at 1 year but did not show increased efficacy for this approach in the second year.11 Several more years worth of data will however need to be collected before we can conclude the booster approach had no impact on immunity. Importantly there were no trends to more serious adverse events in any studies for those in the vaccine group. It is inevitable that different countries will make different decisions around what and who to fund with respect to RSV vaccination based on their own processes and economic evaluations. Importantly no authority has dismissed the published data, with positive recommendations in favour of RSV vaccination particularly in the over 75 age group. The only dissonance in recommendations is in 60–75 year olds without comorbidities where the amount of data is currently too limited to be definitive and this is reflected in more conditional positive recommendations in this group in many guidelines. Given the abundance of data that RSV causes a significant morbidity and mortality burden in our more aged patients and that we now have safe and effective vaccines for them, we can hope that as many as possible will be offered and accept vaccination. It is part of our role as respiratory physicians to encourage them to do so. Open access publishing facilitated by The University of Western Australia, as part of the Wiley - The University of Western Australia agreement via the Council of Australian University Librarians. The author received funding from GSK, Pfizer and Moderna, the companies involved in current RSV vaccines.