Respiratory Syncytial Virus (RSV) Neutralizing Antibodies at Birth Predict Protection from RSV Illness in Infants in the First 3 Months of Life

Abstract

Background Respiratory syncytial virus (RSV) is a leading cause of viral pneumonia and bronchiolitis during the first six months of life. Placentally-transferred antibodies can prevent severe RSV illness, and maternal immunization may reduce illness in young infants. Identifying protective antibody levels will facilitate the advancement of vaccine candidates and maternal immunization. Methods We conducted a nested case-control study involving 587 Malian mother-infant pairs, followed from birth to 6 months of age. RSV cases were infants who developed influenza-like-illness (ILI) or pneumonia and were RSV positive by PCR. Cases were matched to healthy controls and RSV-negative ILI controls. RSV-A and RSV-B neutralizing antibodies were measured in maternal, cord blood, and infant sera at 3 and 6 months of age. Results Maternal antibodies were efficiently transferred to infants. Maternal and infant RSV titers were strongly correlated. Infant antibody titers against RSV-A were 3X higher compared to those against RSV B. At birth, infants who remained healthy had significantly higher RSV-A and RSV-B titers compared to infants that subsequently contracted RSV. RSV-A IC80 titer >239 or RSV-B IC80 titer >60 at birth was significantly associated with being a healthy control compared to an RSV case within the first three months of life. RSV-A IC80 titers in cord blood were associated with decreased episodes of pneumonia. Conclusions Maternally acquired RSV antibodies were associated with protection of infants against community-detected cases of RSV-ILI and pneumonia. RSV antibody levels in cord blood can predict whether an infant will be infected with RSV or remain uninfected.

First-in-Human Trial of a SARS-CoV-2 Recombinant Spike Protein Nanoparticle Vaccine

“…Although these findings have to be cautiously interpreted, they align with the general findings in viral respiratory disease, particularly those infecting via class I fusion proteins such as RSV, that MN responses induced by infections are associated with protection. 21…”

Cord-blood respiratory syncytial virus antibodies and respiratory health in first 5-years of life.

“…Both hospital and community-based studies that have shown higher cord-blood RSV antibody levels are associated with older age at infection, decreased hospitalization, and overall less severe disease 13,[29][30][31] . However, this is not a universal finding and studies in higher-risk populations from Alaska, Kenya, and Nepal have not shown a protective effect for cord-blood antibodies on early RSV infection risk or severity [32][33][34] .…”

Challenges for the Newborn Immune Response to Respiratory Virus Infection and Vaccination

“…Thus, it is possible that the quality of the antibody elicited was insufficient. Maternal antibody-mediated protection of infants has been demonstrated in evaluation of infants born to non-vaccinated pregnant women with protection associated with the level of neutralizing antibody [ 190 , 191 , 192 ]. Nonetheless, in addition to neutralization, other properties of antibody can contribute to its in vivo efficacy including avidity, epitope specificity, glycosylation, and Fc-mediated functional activity.…”

“…However, this is admittedly a major challenge due to the naïve status and immune responsiveness of the infant. When the time frame required to develop a peak response followed by boosting is taken into account, the first dose of vaccine would likely need to be administered within the first few months of life to optimally protect the infant since maternal antibodies start to decline soon after birth with a half-life of 1.5–3 months [ 83 , 178 , 192 ]. The potential impact of maternal antibodies on eliciting a response in newborns following vaccination of newborns is not insignificant and will be discussed below.…”