Abstract
Protective antibody levels are critical for protection from severe enterovirus 71 infection. However, little is known about the specificities and functional properties of the enterovirus 71-specific antibodies induced by natural infection in humans. Here we characterize 191 plasmablast-derived monoclonal antibodies from three enterovirus 71-infected children, each of whom shows a distinct serological response. Of the 84 enterovirus 71-specific antibodies, neutralizing antibodies that target the rims and floor of the capsid canyon exhibit broad and potent activities at the nanogram level against viruses isolated in 1998–2016. We also find a subset of infected children whose enterovirus 71-specific antibodies are focused on the 3- and 2-fold plateau epitopes localized at the margin of pentamers, and this type of antibody response is associated with lower serum titers against recently circulating strains. Our data provide new insights into the enterovirus 71-specific antibodies induced by natural infection at the serological and clonal levels.
Highlights
Protective antibody levels are critical for protection from severe enterovirus 71 infection
A polyclonal antibody response focused on the margin of the Enterovirus 71 (EV71) capsid pentamers was detected in donors Y and Z, and this response was associated with low neutralization titers
The influence of physiological age-related variation on the clonality and specificity of the EV71-specific antibody response should be trivial in our donors, because older children, unlike new-borns and infants, have developed an efficient adaptive immune system for responding to T cell-dependent antigens[13, 47,48,49]
Summary
Protective antibody levels are critical for protection from severe enterovirus 71 infection. We find a subset of infected children whose enterovirus 71-specific antibodies are focused on the 3- and 2-fold plateau epitopes localized at the margin of pentamers, and this type of antibody response is associated with lower serum titers against recently circulating strains. The emergence of novel EV71 strains and genotypes could be due to viral evasion of host immunity This notion is firstly supported by longitudinal and population-scale serological studies showing that a lack of protective antibody levels was responsible for the high infection rate and increased risk of severe illness in young children in the genotype C2 EV71 outbreak in Taiwan in 199813. Residue 145 on the surface of VP1 has been identified as a key antigenic determinant of strain-specific murine mAbs[32] Such mAbs do not necessarily reflect the naturally acquired EV71specific antibody repertoire in children. No human EV71-specific mAbs have been reported; the neutralizing epitopes targeted by the human antibody response during acute EV71 infection are undetermined
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