Abstract
Maternal anti-respiratory syncytial virus (RSV) antibodies acquired by the fetus through the placenta protect neonates from RSV disease through the first weeks of life. In the cotton rat model of RSV infections, we previously reported that immunization of dams during pregnancy with virus-like particles assembled with mutation stabilized pre-fusion F protein as well as the wild type G protein resulted in robust protection of their offspring from RSV challenge. Here we describe the durability of those protective responses in dams, the durability of protection in offspring, and the transfer of that protection to offspring of two consecutive pregnancies without a second boost immunization. We report that four weeks after birth, offspring of the first pregnancy were significantly protected from RSV replication in both lungs and nasal tissues after RSV challenge, but protection was reduced in pups at 6 weeks after birth. However, the overall protection of offspring of the second pregnancy was considerably reduced, even at four weeks of age. This drop in protection occurred even though the levels of total anti-pre-F IgG and neutralizing antibody titers in dams remained at similar, high levels before and after the second pregnancy. The results are consistent with an evolution of antibody properties in dams to populations less efficiently transferred to offspring or the less efficient transfer of antibodies in elderly dams.
Highlights
Respiratory syncytial virus (RSV) is a very common cause of severe acute lower respiratory tract infections in infants and young children, infections that frequently result in hospitalization and, in developing countries, significant mortality [1,2,3]
In a cotton rat model, we have previously shown that maternal immunization with virus-like particles assembled with the RSV F and G proteins protects offspring from RSV infection
Vaccine development has focused on the RSV F protein which is more conserved across all strains of RSV than the G protein and should induce protective responses across all strains
Summary
Respiratory syncytial virus (RSV) is a very common cause of severe acute lower respiratory tract infections in infants and young children, infections that frequently result in hospitalization and, in developing countries, significant mortality [1,2,3]. The early failures to identify an effective vaccine were due, in part, to a lack of recognition that the pre-fusion conformation of the RSV F protein induces optimal protective responses and that this form of F protein is unstable [4,5]. Another issue is a significant concern about vaccine safety of all candidates stemming from the failure of formaldehyde treated virus (FI-RSV), an early vaccine candidate. FI-RSV was ineffective in protecting from disease but, more importantly, resulted in life-threatening enhanced respiratory disease (ERD) upon subsequent exposure to infectious RSV [6,7,8,9]
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