Periodic Reporting for period 2 - PROMISE (Preparing for RSV Immunisation and Surveillance in Europe)
Reporting period: 2023-02-01 to 2024-04-30
RSV causes severe disease in the very young and elderly and results in substantial healthcare costs. In the last 7 years, substantial progress has been made in development of products for active and passive immunisation against RSV, with 4 novel products licensed for use in human populations and additional 21 products currently in clinical development. RSV immunization has been recommended in pregnant people, young infants and older adults in several countries in Europe. PROMISE’s vision is to seamlessly build on, exploit, and add value to the significant achievements of RESCEU to prepare for the imminent introduction of RSV immunisation products. PROMISE comprises of 5 WPs. WP1 conducted epidemiological and cost-effectiveness analyses marshalling data from systematic reviews; national and regional disease registries; surveillance programmes and linked routine healthcare datasets. WP2 fostered a consensus and developed an operational plan for expanded coordinated RSV surveillance and reporting activities; post-licensure monitoring and evaluation of products for RSV immunisation across Europe. WP3 initiated new prospective studies to address key gaps in existing knowledge and assembled biobank for biomarker validation. WP4 validated temporally and at mucosal level biomarkers that were identified in RESCEU adopting state of the art technologies. PROMISE developed high-quality, sustainable, robust data collection systems that linked closely with public health/regulatory bodies/health care providers for informing policy and regulatory processes.
In WP1, we analysed published and unpublished data on RSV seasonality by subgroup and its drivers from 36 sites in 20 countries. The findings are now published in JID shorturl.at/IIrp3. We analysed data from 61 studies from 19 countries to assess the impact of COVID-19 on RSV hospitalisation globally. We found that a significantly higher proportion of children aged 12-24 months were hospitalised with RSV-associated ALRI in high- and upper-middle-income countries during the pandemic years than in 2019. No consistent changes in disease severity were observed DOI: 10.1016/S1473-3099(23)00630-8. This was also observed in our prospective study in 4 EU hospitals DOI: 10.1093/infdis/jiae292. We also published the 1st global analysis of RSV burden in pregnant persons and reported that pooled incidence in this sub-population was 26/1000 person years; and 3.4% of nasopharyngeal swabs from ARI patients in this group are positive for RSV DOI: 10.1093/infdis/jiad449. PROMISE developed a modified RSV bronchiolitis severity score that has been validated externally in 2 small retrospective datasets DOI: 10.1093/infdis/jiad388 as well as in a prospective cohort of 73 infants. We developed a “Rules of Collaboration” document that provided a framework for engagement while discussing sensitive topics in the context of a public private partnership and has enabled public organisations outside the consortium (NITAGs, WHO, ECDC, EMA) to engage with PROMISE. As WP2, PROMISE European RSV Surveillance Bulletins were published fortnightly during winter 23-24 shorturl.at/9xMLw and 2 generic protocols on measuring effectiveness of maternal RSV vaccines and monoclonal antibodies were published doi.org/10.1093/infdis/jiad484; doi.org/10.1093/infdis/jiad483. PROMISE RSV-LabNet developed a working group (from 9 European laboratories) for genotype harmonization and has played an important role in the larger global effort to develop an RSV genotype standard for RSV sequencing which will be necessary for RSV molecular epidemiology. A paper from the global group was published in EID Journal DOI: 10.3201/eid3008.240209. A report on Generic protocols for post-marketing safety studies of preventive products against RSV has been submitted to IMI and the final report to identify RSV immunisation barriers from the 2 surveys was published shorturl.at/Q4LgM. WP3 recruited eligible children from the RESCEU birth cohort and infant case-control studies for the PROMISE long-term follow-up study to determine the relationship between RSV infection during infancy and asthma/wheezing at school age. Additionally, they collected clinical data from infants with RSV infection of different severity; and collected samples from infants recruited for the PROMISE case-control validation study. They also analyzed data from 97 infants with non-medically attended RSV episodes and found that parents reported impairment in usual daily activities, worries, anxiety and work absenteeism DOI: 10.1093/infdis/jiad477. WP4 published a literature review on the humoral immunity to RSV in children DOI: 10.1183/16000617.0106-2024 and completed the analysis of serological assays using samples from the Lowenkids birth cohort. Separately, we found that RSV-induced interferon response extends from the airways to the peripheral blood; and that RSV induces a migration-promoting transcriptional program in monocytes DOI: 10.1093/infdis/jiad487. The consortium has been actively disseminating our analytic plans and interim results through posters and talks at major RSV-related conferences.
PROMISE will form the platform for upcoming future actions on RSV and even other respiratory pathogens that are identified as a priority for action in Europe. Despite several manuscripts are yet to be published, and the full impact may only be measured later, promising signs are well noted to understand the impact of this project. Specifically, during RP2, the modified RSV bronchiolitis severity score developed and validated by WP1 during RP1 was validated prospectively in WP3. Although further validation in retrospective datasets as well as prospective studies may yet be required across several geographies, once sufficiently validated, this could be further used not only in clinical trials but in observational studies too. The RSV severity score would also represent a huge improvement for patient management in a sense that would help identify and triage high-risk patients. PROMISE developed a static multi-cohort model to evaluate the cost-effectiveness of RSV vaccination strategies in older adults, based on the latest available vaccine product and disease burden information. This will help inform NITAGs regarding cost-effectiveness of RSV vaccination. The published RSV bulletin shorturl.at/9yMaz has now been successfully handed over to ECDC and WHO-Europe. We have had meaningful consultation with the EMA and the ECDC coordinated member states NITAGs regarding the 2 generic protocols to study vaccine effectiveness. Consortium members are continuing to support the WHO in their global RSV surveillance efforts. Additionally, PROMISE has successfully developed a data visualisation dashboard to showcase results, and this has been transferred to ReSViNET shorturl.at/iDv0N. We organised a virtual Policy Event which gathered nearly 350 people. The PROMISE PAB and ReSViNET patient network have continued to conduct RSV awareness week in November 2023. During the 3 campaigns throughout the project, we reached more people progressively. All social media channels showed significant growth in the number of followers, especially during the Policy Event. 16 of the PROMISE deliverables have been published as a manuscript (including 14 in the JID academic.oup.com/jid/issue/229/Supplement_1; and we have been actively disseminating our results through posts on social media, posters and talks at major RSV-related conferences.