Respiratory syncytial virus vaccine development
Respiratory syncytial virus (RSV) is a widespread cause of respiratory illness and hospitalizations in infants and children worldwide. Since no vaccine against the virus exists, our RSV vaccine project is working to support the development of RSV interventions to protect the youngest infants from severe disease.
We are concentrating on approaches designed to provide passive immunity, including vaccines that can be used in a maternal immunization strategy to enable antibody transfer from mother to newborn, as well as RSV-specific antibodies administered at birth to provide protection in the first few months of life. We are also supporting research that will help inform RSV control strategies going forward.
In collaboration with developers, universities, government agencies, other research institutions, and international bodies such as the World Health Organization (WHO), our goal is to speed progress toward and ready the enabling environment for such groundbreaking interventions, which could help reduce RSV morbidity and mortality as well as the heavy economic burdens associated with caring for the sick.
Research to support RSV vaccine development efforts
PATH is building on established partnerships and developing new ones to find solutions to relevant scientific and technical issues that support interventions designed to enhance RSV passive immunity in young infants.
Strengthening tools to test RSV vaccines
Current research suggests that antibodies that neutralize RSV could prevent infection, but the variety of neutralization testing in use makes comparing results across vaccine candidates difficult. We are working with assay experts from industry, government, and academia to build the case for creating an international RSV antibody reference standard. The aim is for such a reference standard to ultimately be available through WHO so that vaccine developers have a uniform way to compare RSV vaccines. To inform these efforts, we recently organized a survey study (PDF 312.07 KB) across a diverse range of RSV neutralization assay formats currently in use, which provided evidence that pursuing an international standard is warranted to improve harmonization of assay results.
Though important, neutralizing antibody may not provide the full picture of a vaccine’s performance, so we are also exploring alternate assays that can contribute additional information. To support vaccine development, we are working to make available robust, reproducible, and efficient assays to provide more details about RSV antibody responses to a vaccine.
We also collaborated with both Novartis Vaccines and Diagnostics, Inc. and GlaxoSmithKline Vaccines to develop RSV preclinical models for evaluating RSV vaccine candidates for pregnant women. These studies included developing and optimizing in vivo and in vitro models designed to add to the RSV vaccine development toolbox, and will help inform maternal immunization strategies going forward.
Case building for maternal immunization as an approach to prevent RSV
Other research collaborations evaluated the feasibility of RSV maternal immunization strategies in the developing world. In healthy populations, transfer of maternal protective antibody to the fetus is very efficient. In populations with chronic infections such as malaria or HIV, antibody transfer may not be as efficient.
We are working with Dr. Ruth Karron at the Bloomberg School of Public Health, Johns Hopkins University; Dr. Christopher King at Case Western Reserve University; and Dr. Willie Pomat and colleagues at the Papua New Guinea Institute of Medical Research to assess how malaria present in the placenta affects the transfer of RSV-specific neutralizing antibody from mothers to infants.
With Dr. Janet Englund of Seattle Children’s Research Institute and Dr. Helen Chu of the University of Washington, we studied RSV disease burden as well as the transfer and protective effect of maternal-derived RSV antibody in infants in Bangladesh and Nepal, as well as RSV disease burden in mothers and their infants.
Under an agreement with the University of Warwick, we worked with Dr. James Nokes through the Kenya Medical Research Institute to evaluate the relationship between maternal RSV-specific antibody and protection in infants. We also looked at the rate at which antibody protection declines from birth using samples collected from newborns in Kilifi, Kenya.
Studying the relationship between RSV and asthma in low-resource countries
Infection with RSV early in life appears to correlate with an increased chance of developing recurrent wheezing and asthma. More information is needed to understand this relationship, and we are currently exploring opportunities to fill research gaps in this area.