CHARACTERIZATION OF NEUTRALIZING MONOCLONAL-ANTIBODY ESCAPE MUTANTS OF HANTAAN-VIRUS-76118

Neutralizing monoclonal antibody (MAb) escape mutants of Hantaan virus were generated using MAbs to envelope protein G1 (16D2) and G2 (11E10 ). The mutant viruses (mu16D2 and mu11E10), lacked reactivity only to the selecting MAb, or a MAb belonging to the same antigenic site. Both mutants had a single amino acid (a.a.) substitution. The a.a. substit ution, found in mu16D2, was different from that found in another mutan t selected with the same MAb (16D2). Although MAb 11E10 immunoprecipit ated G2 protein, a deduced a.a. substitution was located in the G1 reg ion. These results suggest that antigenic sites defined by neutralizin g MAbs are composed of discontinuous epitopes over the G1 and G2 prote ins. Mutant 11E10 showed a significant decrease in virulence in suckli ng mice. A virulence revertant of mu11E10, selected through passages i n suckling mice brain, showed exactly the same deduced a.a. sequence a s mu11E10 and still was not neutralized by MAb 11E10. Since mutant 16D 2 was virulent for suckling mice, neutralization related epitopes foun d with MAbs 11E10 and 16D2 were independent of pathogenicity in BALB/c mice.