The uptake and real-world effectiveness of emerging respiratory syncytial virus maternal vaccines and monoclonal antibodies on short- and long-term respiratory morbidities

The National Institute of Allergy and Infectious Diseases (NIAID) awarded Vanderbilt University Medical Center a $3.3 million Project Grant under the Allergy and Infectious Diseases Research program (CFDA 93.855) on August 11, 2025, to examine the real-world effectiveness and uptake of newly approved Respiratory Syncytial Virus (RSV) maternal vaccines and monoclonal antibodies. The research will assess comparative effectiveness, cost-effectiveness, safety, and impact on short- and long-term respiratory morbidities in infants through July 31, 2029. The project will leverage a population of over 735,000 mother-child dyads from the Tennessee Medicaid Program and Department of Defense Military Health System to determine optimal RSV prevention strategies based on infant characteristics, date of birth relative to RSV circulation, and risk factors for RSV lower respiratory tract infection.

The grant involves collaborative research with sub-awardees University of California, Berkeley and University of Arizona, as well as consulting support from Kennell & Associates Inc. The research will determine product uptake and adherence to policy recommendations among maternal and infant populations, conduct real-world effectiveness and comparative analyses of available RSV prevention products, and evaluate cost-effectiveness outcomes. This investigation directly addresses evidence gaps regarding the newly available RSV maternal immunization options approved for use in infants born in 2023 and later, providing critical data to inform maternal and infant vaccination policy and optimize protection strategies against RSV-associated severe illness.

Abstract

Respiratory syncytial virus (RSV) is one of the most common respiratory viruses resulting in significant morbidity and mortality in infants and young children globally. Recent approvals of the world's first maternal vaccine and infant extended half-life monoclonal antibody mean that for the first time, all infants born in the US in 2023 and later will have immunization options for protection from RSV-associated severe illness. The two currently available prevention products differ in target recipients, timing of administration, biologic mechanism of action, and duration of infant protection. As these products have become part of recommended maternal and infant vaccine schedules, key questions needed to inform policy include determining: 1) the real-world comparative effectiveness, 2) the cost-effectiveness of these products, 3) safety of maternal vaccine, and 4) impact on other acute and long-term respiratory outcomes. To address these questions, we propose to assemble a population of over 735,000 mother-child dyads including infants born 2023-2029 utilizing the diverse populations represented by the tennessee medicaid program and department of defense military health system. The overarching objectives are to determine optimal RSV prevention strategy(IES) taking into consideration infant date of birth relative to RSV circulation, infant risk for RSV lrti, maternal- child characteristics, and the effectiveness and cost-effectiveness of RSV prevention products in reducing the risk of RSV lrti, other acute respiratory illness, and later childhood all-cause respiratory morbidity. We will determine the uptake, adherence to policy recommendations, and characteristics of those who receive the approved RSV prevention products (aim 1), the real-world effectiveness and comparative effectiveness in reducing the risk and severity of RSV lrti and other acute respiratory morbidities (aim 2), the effectiveness on reducing later childhood all-cause respiratory morbidity (aim 3), and the cost-effectiveness in reducing RSV lrti and childhood all-cause respiratory morbidity (aim 4) of these RSV prevention products. Socioeconomic associated health disparities at the individual and neighborhood levels in vaccine uptake (aim 1) and effectiveness (aims 2 & 3) will be determined. With supply chain limitations affecting the availability of infant extended half-life monoclonal antibody, the 2023-2024 respiratory season presents a unique opportunity to evaluate these disparities in the setting of the initiation of a large nationwide medical intervention. Results of the study will inform public health expectations and policy recommendations for RSV maternal vaccines and extended half-life monoclonal antibodies, and more importantly, identify and quantify any value-added long- term benefits of RSV lrti prevention during infancy on later childhood respiratory morbidity. We anticipate that this will in turn increase public acceptability, promote uptake of RSV prevention products in the US, and provide data to support the acute and longer-term benefits of these prevention products worldwide, promote uptake of these products worldwide and particularly in low- and middle-income countries.