Real-world effectiveness of perinatal RSV immunoprophylaxis: protocol for a test-negative case-control study.
| Title: | Real-world effectiveness of perinatal RSV immunoprophylaxis: protocol for a test-negative case-control study. |
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| Authors: | Aparicio Llorente C; Yale School of Medicine Department of Pediatrics, New Haven, Connecticut, USA.; Wats A; Yale School of Medicine Department of Pediatrics, New Haven, Connecticut, USA.; Araujo BL; Yale School of Medicine Department of Pediatrics, New Haven, Connecticut, USA.; Moniz Ganem J; Yale School of Medicine Department of Pediatrics, New Haven, Connecticut, USA.; Oliva IO; Yale School of Medicine Department of Pediatrics, New Haven, Connecticut, USA.; Xu H; Yale School of Public Health Department of Epidemiology of Microbial Diseases, New Haven, Connecticut, USA.; Brodsky NN; Yale School of Medicine Department of Pediatrics, New Haven, Connecticut, USA.; Lucas CL; Yale School of Medicine Department of Immunobiology, New Haven, Connecticut, USA.; Aronson PL; Yale School of Medicine Department of Pediatrics, New Haven, Connecticut, USA.; Grubaugh ND; Yale School of Public Health Department of Epidemiology of Microbial Diseases, New Haven, Connecticut, USA.; Breban M; Yale School of Public Health Department of Epidemiology of Microbial Diseases, New Haven, Connecticut, USA.; Redmond S; Yale School of Public Health Department of Epidemiology of Microbial Diseases, New Haven, Connecticut, USA.; Shapiro ED; Yale School of Medicine Department of Pediatrics, New Haven, Connecticut, USA.; Yale School of Public Health Department of Epidemiology of Microbial Diseases, New Haven, Connecticut, USA.; Niccolai LM; Yale School of Public Health Department of Epidemiology of Microbial Diseases, New Haven, Connecticut, USA.; Weinberger DM; Yale School of Public Health Department of Epidemiology of Microbial Diseases, New Haven, Connecticut, USA.; Oliveira CR; Yale School of Medicine Department of Pediatrics, New Haven, Connecticut, USA carlos.oliveira@yale.edu.; Yale School of Public Health Department of Biostatistics, New Haven, Connecticut, USA.; Yale School of Medicine Department of Biomedical Informatics and Data Science, New Haven, Connecticut, USA. |
| Source: | BMJ open [BMJ Open] 2026 Mar 19; Vol. 16 (3), pp. e114524. Date of Electronic Publication: 2026 Mar 19. |
| Publication Type: | Journal Article; Clinical Trial Protocol |
| Language: | English |
| Journal Info: | Publisher: BMJ Publishing Group Ltd Country of Publication: England NLM ID: 101552874 Publication Model: Electronic Cited Medium: Internet ISSN: 2044-6055 (Electronic) Linking ISSN: 20446055 NLM ISO Abbreviation: BMJ Open Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: [London] : BMJ Publishing Group Ltd, 2011- |
| MeSH Terms: | Respiratory Syncytial Virus Infections*/prevention & control ; Respiratory Syncytial Virus Infections*/immunology ; Respiratory Syncytial Virus, Human*/immunology ; Respiratory Syncytial Virus, Human*/genetics ; Respiratory Syncytial Virus Vaccines*; Humans ; Case-Control Studies ; Infant ; Female ; Infant, Newborn ; Vaccine Efficacy ; Research Design ; Male |
| Abstract: | Introduction: Respiratory syncytial virus (RSV) is a leading cause of hospitalisation in infants worldwide. New immunoprophylactic products, including long-acting monoclonal antibodies and maternal vaccines, have demonstrated high efficacy in prelicensure clinical trials. Understanding how these interventions perform outside controlled trials, and how viral evolution or host factors influence protection, is essential for sustaining confidence in RSV prevention programmes.; Methods and Analysis: We will conduct a 5-year, test-negative case-control study among infants ≤12 months of age who present with acute respiratory illness (ARI) within a large healthcare delivery network serving a demographically diverse population. Cases will be infants testing positive for RSV by PCR, and controls will be RSV-negative infants meeting the same ARI criteria. Data will be obtained from electronic health records, structured caregiver surveys and state immunization registries to ensure accurate classification of exposures and covariates. Vaccine effectiveness will be estimated using multivariable logistic regression controlling for potential confounding. RSV-positive specimens will undergo full-genome sequencing to identify variant lineages and potential immune-escape mutations. A subset of participants will provide acute and convalescent blood samples for single-cell immune profiling to define innate and adaptive responses associated with breakthrough infection.; Ethics and Dissemination: The study protocol has been approved by the Yale Human Investigation Committee (HIC #2000036550). Written informed consent will be obtained from all parents or legal guardians prior to participation. Study findings will be disseminated through peer-reviewed publications, scientific meetings and public repositories, with fully de-identified participant data to protect privacy and confidentiality. Viral genomic data will be shared in accordance with the National Institutes of Health Genomic Data Sharing Policy, and analytical code will be made publicly available to ensure reproducibility.; Trial Registration Number: NCT06172660.; (© Author(s) (or their employer(s)) 2026. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group.) |
| Competing Interests: | Competing interests: Potential conflict of interest: Dr LN has served as a scientific advisor for Merck and Moderna (both unrelated to this work). Dr DMW has been the principal investigator on grants from Pfizer and Merck to Yale University for work unrelated to this manuscript and has received consulting fees from Pfizer, Merck and GSK for work unrelated to this manuscript. Dr PA is the principal investigator on a grant from Merck that aims to increase parental confidence in newborn RSV immunoprophylaxis administration. All other authors declare no conflicts of interest. |
| Contributed Indexing: | Keywords: Case-Control Studies; Immunization Programs; Paediatric infectious disease & immunisation; Respiratory Syncytial Virus, Human |
| Molecular Sequence: | ClinicalTrials.gov NCT06172660 |
| Substance Nomenclature: | 0 (Respiratory Syncytial Virus Vaccines) |
| Entry Date(s): | Date Created: 20260319 Date Completed: 20260319 Latest Revision: 20260325 |
| Update Code: | 20260326 |
| PubMed Central ID: | PMC13007147 |
| DOI: | 10.1136/bmjopen-2025-114524 |
| PMID: | 41856594 |
| Database: | MEDLINE |
Journal Article; Clinical Trial Protocol