Human memory B cells producing potent cross-neutralizing antibodies against human parechovirus; implications for prevalence, treatment and diagnosis

摘要: UNLABELLED The family Picornaviridae is a large and diverse group of positive-sense RNA viruses, including human enteroviruses (EVs) parechoviruses (HPeVs). immune response against EVs HPeVs thought to be mainly humoral, an insufficient neutralizing antibody (Ab) during infection risk factor can ultimately life threatening. accessibility different antigenic sites observed cross-reactivity make good target for development therapeutic monoclonal antibodies (MAbs). In this study, we generated two MAbs specific HPeV by screening culture supernatants Ab-producing B cell cultures direct neutralization HPeV1. Both showed HPeV1-specific as well HPeV2. One antibody, AM18, cross-neutralized HPeV4, -5, -6 coxsackievirus A9 (CV-A9). VP1 capsid protein-specific assays confirmed that AM18 bound HPeV1, -2, -4 with high affinity (11.5 pM). contrast, the MAb AM28, which neutralized HPeV1 even more efficiently than did no HPeV3 or other not bind any proteins, suggesting AM28 conformation-dependent, nonlinear epitope on virus. discovery are cross-reactive between may help treatment options vaccine design based epitopes recognized these antibodies. IMPORTANCE infections widespread among young children adults, causing broad range disease. Infections severe threatening, while antiviral available. Given absence Abs disease in infants, picornavirus would option. To study detail, MAbs. show also HPeVs. Surprisingly, CV-A9. These provide unique tool further research diagnosis (antigen detection) possible infections.