Related Experiment Video
Updated: Mar 21, 2026
An Improved and High Throughput Respiratory Syncytial Virus RSV Micro-neutralization Assay
Published on: January 26, 2019
Real-world effectiveness of perinatal RSV immunoprophylaxis: protocol for a test-negative case-control study
Camila Aparicio Llorente1, Aanchal Wats1, Barbara L Araujo1
1Yale School of Medicine Department of Pediatrics, New Haven, Connecticut, USA.
Insights
This study will evaluate the real-world effectiveness of new respiratory syncytial virus (RSV) prevention methods in infants. It will also investigate how RSV strains and immune responses impact protection, crucial for public health strategies.
Area of Science:
- * Pediatric Infectious Diseases
- * Immunology
- * Public Health Virology
Background:
- * Respiratory syncytial virus (RSV) is a major cause of infant hospitalizations globally.
- * New immunoprophylactic interventions, including monoclonal antibodies and maternal vaccines, show promise in clinical trials.
- * Real-world data on intervention effectiveness and the influence of viral evolution and host factors are crucial for sustained RSV prevention.
Purpose of the Study:
- * To assess the effectiveness of novel RSV immunoprophylactic products in a real-world setting.
- * To investigate the impact of viral genetic diversity and host immune profiles on RSV protection.
- * To inform ongoing public health strategies for RSV prevention in infants.
Main Methods:
- * A 5-year test-negative case-control study involving infants up to 12 months old presenting with acute respiratory illness (ARI).
- * Cases are RSV-positive infants; controls are RSV-negative infants with ARI.
- * Data collection includes electronic health records, caregiver surveys, and immunization registries, supplemented by full-genome sequencing of RSV and immune profiling via blood samples.
Main Results:
- * This section will report on the estimated vaccine effectiveness using multivariable logistic regression.
- * Analysis will identify RSV variant lineages and potential immune-escape mutations.
- * Innate and adaptive immune responses associated with breakthrough RSV infections will be characterized.
Conclusions:
- * Findings will provide critical real-world evidence on the effectiveness of new RSV interventions.
- * Understanding viral evolution and host immunity will enhance RSV prevention strategies.
- * The study aims to ensure sustained confidence in global RSV prevention programs.
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.
