Human recombinant neutralizing antibodies against hantaan virus G2 protein.
Old world hantaviruses, causing hemorrhagic fever with renal syndrome (HFRS), still present a public health problem in Asia and Eastern Europe. The majority of cases has been recorded in China. The aim of our study was to generate human recombinant neutralizing antibodies to a hantavirus by phage display technology. To preserve the structural identity of viral protein, the panning procedure was performed on native Hantaan (HTN) (76-118) virus propagated in Vero-E6 cells. In total, five complete human recombinant IgG antibodies were produced in a baculovirus expression system. All of them were able to completely neutralize HTN, and Seoul (SEO) virus in a plaque reduction neutralization test (PRNT). Three of these antibodies could also completely neutralize Dobrava (DOB) virus but not Puumala (PUU) virus. All antibodies bind to Hantaan virus G2 protein localized in the virus envelope. The sequence areas within the HTN (76-118)-G2 protein detected by five selected antibodies were mapped using peptide scans. Two partial epitopes, 916-KVMATIDSF-924 and 954-LVTKDIDFD-963, were recognized, which presumably are of paramount importance for docking of the virus to host cell receptors. A consensus motif 916-KVXATIXSF-924 could be identified by mutational analysis. The neutralizing antibodies to the most widely distributed hantaviruses causing HFRS might be promising candidates for the development of an agent for prevention and treatment of HFRS in patients.
Koch
Joachim
J
Hantavirus-Forschungsstelle der Heidelberger Akademie der Wissenschaften, Im Neuenheimer Feld 230, D-69120 Heidelberg, Germany. joachim.koch@em.uni-frankfurt.de
Liang
Mifang
M
Queitsch
Iris
I
Kraus
Annette A
AA
Bautz
Ekkehard K F
EK
D000595:Amino Acid Sequence; D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D000918:Antibody Specificity; D016367:Baculoviridae / Q000378:metabolism; D001666:Binding Sites, Antibody / Q000235:genetics; D002522:Chlorocebus aethiops; D016384:Consensus Sequence; D018604:Epitope Mapping; D000939:Epitopes / Q000235:genetics; D005822:Genetic Vectors; D018063:Hantaan virus / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000276:immunology; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D019151:Peptide Library; D011994:Recombinant Proteins / Q000276:immunology; D016415:Sequence Alignment; D014709:Vero Cells; D014759:Viral Envelope Proteins / Q000235:genetics / Q000276:immunology*
D000914:Antibodies, Viral; D000939:Epitopes; D007074:Immunoglobulin G; D019151:Peptide Library; D011994:Recombinant Proteins; D014759:Viral Envelope Proteins; C090197:glycoprotein G2, Hantavirus