Respiratory syncytial virus (RSV) is a leading cause of respiratory illness in children and older adults. In most healthy adults, infection causes a mild cold-like illness with recovery in one to two weeks. However, in infants and the elderly, RSV often causes severe bronchiolitis and pneumonia. Currently, there is no vaccine against RSV infection and only limited therapies, especially in resource-limited countries. One problem with protection of infants is that they have immature immune systems. To compensate for the developing immune system, maternal antibodies are transferred to infants through the placenta. These antibodies are thought to help protect babies until their own immune system matures. To investigate the possibility of vaccinating mothers to protect against early infant infection, a cohort of mothers and infants in rural Nepal were studied. By collecting matched maternal and cord blood samples and sampling RSV antibodies, the researchers hoped to provide insight into antibody titers and RSV infection/outcome. The results of this inquiry were published in the Journal of Clinical Virology by a collaborative group including Fred Hutch (Vaccine and Infectious Disease Division) and University of Washington researchers.
The group analyzed matched blood from over 300 mother-infant pairs from Nepal (see figure). RSV antibody titer was measured in both sample sets. The concentrations of antibody in both the maternal blood and the cord blood (collected at the time of birth) were similar (11.3 and 11.2 log2, respectively) and highly correlated. In this cohort, 30 infants (9%) ultimately showed symptoms of RSV infection. In comparing the infants with and without RSV infection, the group looked at both maternal and cord blood titers. They found that maternal antibody levels were similar in both groups but that infants with RSV had cord blood levels of 12.1 versus 11.6 of non-infected. Interestingly, the antibody transfer ratio was higher in infants with RSV compared to those without. Looking closer at maternal transfer rate, the researchers found no impact in transfer ratio by maternal age, education, breastfeeding, or household smoking. However, the sex of the infant was associated with the transfer ratio, with male infants having a lower rate. Increased gestational time was also associated with increased transfer.
Image provided by Dr. Chu.
In total, this longitudinal study assessed mother-infant pairs and the effect of maternal antibodies on infant RSV infection rates and found that natural infection of mothers and subsequent antibody transfer was not enough to affect RSV acquisition. We know that high titer neutralizing antibody, when administered post infection, can treat RSV, and together with this paper’s results, the data suggest that the mother’s natural response may not be enough and that vaccinating pregnant mothers may boost maternal antibody titer and thus infant antibody transfer. The future of this project includes collecting data from many more matched mother-infant pairs. The researchers are currently planning a much larger study, with 1500 pairs from Nepal. Procedures will include reporting and sampling all illnesses, both by PCR and antibody samples, collecting matched blood, and similar in-house visits.
This research was supported by the National Institutes of Allergies and Infectious Disease, NIH and the Bill and Melinda Gates Foundation.
Chu HY, Tielsch J, Katz J, Magaret AS, Khatry S, LeClerq SC, Shrestha L, Kuypers J, Steinhoff MC, Englund JA. 2017. Transplacental transfer of maternal respiratory syncytial virus (RSV) antibody and protection against RSV disease in infants in rural Nepal. J Clin Virol, 95, 90-95.