Characteristics of RSV-Specific Maternal Antibodies in Plasma of Hospitalized, Acute RSV Patients under Three Months of Age

Abstract

Respiratory syncytial virus (RSV) is the leading cause for respiratory illness that requires hospitalization in infancy. High levels of maternal antibodies can protect against RSV infection. However, RSV-infected infants can suffer from severe disease symptoms even in the presence of high levels of RSV-specific antibodies. This study analyzes several serological characteristics to explore potential deficiencies or surpluses of antibodies that could relate to severe disease symptoms. We compare serum antibodies from hospitalized patients who suffered severe symptoms as well as uninfected infants. Disease severity markers were oxygen therapy, tachypnea, oxygen saturation, admission to the intensive care unit and duration of hospitalization. Antibodies against RSV G protein and a prefusion F epitope correlated with in vitro neutralization. Avidity of RSV-specific IgG antibodies was lower in RSV-infected infants compared to uninfected controls. Severe disease symptoms were unrelated to RSV-specific IgG antibody titers, avidity of RSV-IgG, virus neutralization capacity or titers against pre- and postfusion F or G protein ectodomains and the prefusion F antigenic site Ø. In conclusion, the detailed serological characterization did not indicate dysfunctional or epitope-skewed composition of serum antibodies in hospitalized RSV-infected infants suffering from severe disease symptoms. It remains unclear, whether specific antibody fractions could diminish disease symptoms.

Natural killer cell activation by respiratory syncytial virus-specific antibodies is decreased in infants with severe respiratory infections and correlates with Fc-glycosylation

“…As expected, there was a positive correlation between the concentrations of antibodies targeting different RSV antigens, as exemplified for pre-F and G A ( Fig 1D ). The concentrations of antigen-specific antibodies did not significantly differ between RSV-infected cases, uninfected controls, and RSV-negative infected controls ( Fig 2A-D ), confirming previous findings in a subset of this cohort (12).…”

“…Some studies show that high RSV-specific maternal antibody titers are associated with protection against RSV infection or (severe) disease (5-8). In contrast, other studies do not show a protective effect (9-12) or even indicate an association between high maternal antibody titers and an increased risk of recurrent wheezing (13). Strikingly, the vast majority of studies investigating the role of (maternal) antibodies in RSV infection only look at in vitro binding or neutralization capacity, while additional antibody effector functions are not taken into account.…”

Natural killer cell activation by respiratory syncytial virus‐specific antibodies is decreased in infants with severe respiratory infections and correlates with Fc‐glycosylation

“…As expected, there was a positive correlation between the concentrations of antibodies targeting different RSV antigens, as exemplified for pre‐F and G A (Figure d). The concentrations of antigen‐specific antibodies did not significantly differ between RSV‐infected cases, uninfected controls and RSV‐negative infected controls (Figure a–d), confirming previous findings in a subset of this cohort …”

“…The concentrations of antigen-specific antibodies did not significantly differ between RSV-infected cases, uninfected controls and RSVnegative infected controls ( Figure 2a-d), confirming previous findings in a subset of this cohort. 12…”

“…Some studies show that high RSV‐specific maternal antibody titres are associated with protection against RSV infection or (severe) disease . In contrast, other studies do not show a protective effect or even indicate an association between high maternal antibody titres and an increased risk of recurrent wheezing . Strikingly, the vast majority of studies investigating the role of (maternal) antibodies in RSV infection only look at in vitro binding or neutralisation capacity, while additional antibody effector functions are not taken into account.…”