An elaborate landscape of the human antibody repertoire against enterovirus 71 infection is revealed by phage display screening and deep sequencing

Abstract

Enterovirus 71 (EV71) causes outbreaks of hand, foot and mouth disease (HFMD), primarily in the Asia-Pacific area, that are often associated with complications of severe to fatal neurological symptoms. There are currently no anti-viral therapies or vaccines available for the treatment of EV71 infection. Illustrating human antibody responses neutralizing EV71 infection could potentially provide valuable information for the development of effective therapies and vaccines. Here, we constructed a comprehensive phage display library based on peripheral blood of eight EV71-infected donors and identified 27 EV71-specific human antibodies, of which four have neutralizing activity in in vitro experiments. Deep sequencing analysis of the antibody heavy chains at the transcript level of another three independent EV71-infected donors and three controls demonstrates that heavy chains of the EV71-specific antibodies are conserved among EV71-infected individuals but absent in controls, suggesting convergent evolution of human antibodies against EV71.