Premature infants may not be adequately protected by new RSV vaccines given to their mothers during pregnancy. The vaccines were tested mainly in full-term babies from low-risk pregnancies, leaving critical gaps in knowledge. This PhD will take blood and nasal samples from infants at birth and six months old, comparing immune responses between premature and full-term babies, and between those whose mothers were vaccinated before or after a specific point in gestation. It will also analyse NHS hospital data to see whether maternal vaccination actually prevents RSV hospital admissions in premature infants. If successful, the research could change national vaccination policy by identifying the optimal timing for maternal RSV vaccination and confirming whether preterm infants—who face the highest risk of severe RSV—are genuinely protected. This would directly reduce hospital admissions, intensive care stays, and long-term wheezing episodes in the most vulnerable newborns, improving outcomes for a group that current vaccine trials largely overlooked.
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Background. Respiratory syncytial virus (RSV) contributes to 33 million acute respiratory infections and 101,400 deaths annually in children under 5 years old. Infants under one are at higher risk, especially those born prematurely, and those with immune deficiency and/or congenital heart disease. New maternal vaccines have shown 81.8% efficacy in reducing RSV lower respiratory infection. However, these data are derived from predominantly term infants born from low-risk pregnancies, therefore important questions remain, including 1) whether premature infants are adequately protected by maternal vaccination 2) the optimal gestation of vaccination in pregnancy. This PhD aims to evaluate: i) immunological markers of RSV protection amongst premature vs term infants born to mothers vaccinated against RSV; ii) infants' immunological markers of RSV protection based on timing of maternal vaccination; and iii) the impact of maternal vaccination on clinical outcomes of premature infants. Methods This proposal includes two sub-studies, an immunological study and an epidemiological analysis of English NHS surveillance data. The immunological study will be conducted as a new sub-study of the BaBi (Born and Bred in) cohort study. 272 BaBi participants will be invited to a new sub-study across four groups: Infants born to mothers i) vaccinated against RSV before 32 weeks gestation, ii) vaccinated against RSV after 32 weeks gestation, iii) vaccinated against RSV and where the infant is subsequently born preterm, and iv) unvaccinated against RSV. Blood and nasal samples will be taken at birth and 6 months of life, and evaluated for i) Anti-RSV F protein IgG antibodies, ii) Anti-RSV G protein IgG, iii) Anti-RSV IgM, iv) Anti-RSV IgA assessed using in-house and commercial Enzyme-linked immunosorbent assays (ELISA). The epidemiological analysis will include analysis of routinely collected national data (RSV samples and medical attendances) using electronic databases in the UKHSA (Datamart, Secondary Uses Survey and Hospital Episode Statistics). The primary laboratory outcome will be difference in anti RSV serum IgG geometric mean titres at birth and 6 months between premature and term infants and between infants whose mothers were vaccinated from 32 weeks and before 32 weeks gestation. The primary epidemiological outcome will be whether premature infants are protected against RSV hospital admission following maternal vaccination. Anonymised, linked data will be analysed to compare impact of RSV vaccination in reducing hospital admissions, high dependency care/ intensive care admissions, and subsequent wheeze episodes up to 24 months for any respiratory tract condition associated with a positive RSV test based on preterm vs term infants. The study was informed by consultation with patient families. Summary: This PhD combines serological and epidemiological approaches to understand the optimal gestation of RSV maternal vaccination and evaluate how well maternal vaccines protect premature infants. This will provide training in research protocols, recruitment, analysis, and participant engagement and involvement of participants in research. This aims to inform national policy on how to protect premature infants and optimum timing of vaccination, and ultimately to reduce the burden of RSV disease.
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