Key result
A novel EV-A71 mutant with substitutions at VP1-98K, 145Q, and 164E exhibited reduced neutralization against human antisera and substantially increased binding ability to human cells.
Specific mutations in the EV-A71 VP1 capsid protein reduce neutralization by human antisera and increase cell binding, highlighting the need for surveillance to ensure vaccine efficacy.
EV-A71 VP1 mutants may evade neutralization; leaves open whether vaccines require updating against emerging strains.
UNLABELLED: Human enterovirus A71 (EV-A71) belongs to the Enterovirus A species in the Picornaviridae family. Several vaccines against EV-A71, a disease causing severe neurological complications or even death, are currently under development and being tested in clinical trials, and preventative vaccination programs are expected to start soon. To characterize the potential for antigenic change of EV-A71, we compared the sequences of two antigenically diverse genotype B4 and B5 strains of EV-A71 and identified substitutions at residues 98, 145, and 164 in the VP1 capsid protein as antigenic determinants. To examine the effects of these three substitutions on antigenicity, we constructed a series of recombinant viruses containing different mutation combinations at these three residues with a reverse genetics system and then investigated the molecular basis of antigenic changes with antigenic cartography. We found that a novel EV-A71 mutant, containing lysine, glutamine, and glutamic acid at the respective residues 98, 145, and 164 in the VP1 capsid protein, exhibited neutralization reduction against patients' antisera and substantially increased virus binding ability to human cells. These observations indicated that this low-neutralization-reactive EV-A71 VP1-98K/145Q/164E mutant potentially increases viral binding ability and that surveillance studies should look out for these mutants, which could compromise vaccine efficacy. IMPORTANCE: Emerging and reemerging EV-A71 viruses can cause severe neurological etiology, primarily affecting children, especially around Asia-Pacific countries. We identified a set of mutations in EV-A71 that both reduced neutralization activity against humoral immunity in antisera of patients and healthy adults and greatly increased the viral binding ability to cells. These findings provide important insights for EV-A71 antigenic determinants and emphasize the importance of continuous surveillance, especially after EV-A71 vaccination programs begin.
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Huang et al. (2015) studied Enterovirus A71 infection. EV-A71 VP1-98K/145Q/164E mutant vs. Wild-type EV-A71 strains was evaluated on Neutralization reduction and cell binding ability. A novel EV-A71 mutant with substitutions at VP1-98K, 145Q, and 164E exhibited reduced neutralization against human antisera and substantially increased binding ability to human cells.
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