Epitope-associated and specificity-focused features of EV71-neutralizing antibody repertoires from plasmablasts of infected children

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.

High-Frequency, Functional HIV-Specific T-Follicular Helper and Regulatory Cells Are Present Within Germinal Centers in Children but Not Adults

“…Whether children make superior antibodies to adults per se is unclear and is complicated both by exposure that, for most common infections, occurs in childhood, and the influence of maternal antibodies. Infants infected with Rota virus, display superior neutralizing antibody responses greater than their mothers ( 69 ), and potent cross-clade neutralizing antibody responses against Enterovirus exist in children ( 70 ). However, children do not appear to make neutralizing antibodies to Influenza A H5/N1 infection, whilst adults do ( 71 ).…”

Epidemic dynamics, interactions and predictability of enteroviruses associated with hand, foot and mouth disease in Japan

“…For EV-A71 and CV-A16, differences in replication capability have been noted in cells in vitro . The assumption of lifelong homotypic immunity against non-polio enteroviruses also needs to be tested [ 68 , 69 ]. For polio, serum IgG neutralizing antibodies (believed to be maintained for life) prevent infection from progressing to viraemia, while IgA-mediated mucosal immunity prevents infection by limiting replication of the virus inside the intestine.…”

Seroprevalence of antibodies to enterovirus 71 and coxsackievirus A16 among people of various age groups in a northeast province of Thailand

“…It is reported that VP1, VP2 and VP3 capsid proteins all contain neutralizing epitopes, but that VP1 contains the major neutralizing domain [ 43 , 44 ]. Our analysis on intra-subgenotypic variation demonstrated that there were 3 amino acid differences (position 239 in VP2, and positions 663 and 857 in VP1) among 3 strains within the B5 subgenotype; and there were 4 positions of difference between 2 strains of the C4a subgenotype (positions 545 and 557 in VP3, and positions 805 and 814 in VP1).…”