Infants Infected with Respiratory Syncytial Virus Generate Potent Neutralizing Antibodies that Lack Somatic Hypermutation

Goodwin E, et al.,, Immunity, 2018

Respiratory syncytial virus (RSV) causes bronchiolitis and pneumonia in infants and elderly. It is a major cause of death among infants. Understanding the infant antibody responses to RSV infection is of great importance in order to develop an effective RSV vaccine. Most of the RSV vaccination strategies use neutralizing antibodies that target the RSV fusion glycoprotein (RSV F). RSV F mediates the initial phases of viral infection by transforming from a prefusion conformation (preF) to a highly stable postfusion conformation (postF). Reported herein is the characterization of the infant antibody response to RSV F by isolating more than 450 RSV F-specific antibodies from seven RSV-infected infants. Bio-Layer Interferometry (BLI) was used to study the binding affinities of IgGs towards DS-Cav1 (RSV prefusion F) and RSV F ΔFP (RSV postfusion F). A Pall ForteBio Octet HTX system equipped with Anti-Human IgG Fc (AHQ) was used to perform all BLI assays. AHQ sensor tips were immobilized with IgGs and dipped into wells containing antigens for an association step, followed by a dissociation step in the buffer. The BLI data obtained were fitted to a 1:1 binding model. The association rate constants, dissociation rate constants, and KD values were determined. Collectively, the results of this study demonstrate that the infant antibody responses to RSV F differ significantly from those of healthy adults and highlight the importance of developing age-specific RSV vaccines.

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