Correlation between epitopes on hemagglutinin of measles virus and biological activities: passive protection by monoclonal antibodies is related to their hemagglutination inhibiting activity

Abstract

Measles virus monoclonal antibodies (MoAbs) were used to investigate the structure of the hemagglutinin (H) antigen, in order to study the regions of the molecule implicated in protection. Using a competition binding assay, three overlapping domains were defined, and these have been correlated with the biological activities of their corresponding MoAb. All of the anti-H MoAbs, with a single exception, neutralized virus infectivity in vitro. We investigated their capacity in passive protection using a measles virus-mouse model, in which inoculated newborn mice died of an acute encephalitis. The course of the disease was monitored after passive administration of the MoAbs, and from their activity, these MoAbs could be divided in three groups: I--protective, II--inducer of a retarded disease, III--nonprotective. The isotype of the antibody did not play a direct role in determining the course of the disease. Moreover, we were able to correlate protection with biological activity of the MoAbs. Only the MoAbs which inhibit hemagglutination activity (HI) protected against the acute disease. Measles MoAbs which neutralize canine distemper virus (CDV) in vitro failed to passively protect CDV-infected mice against disease. These results suggest an immune mechanism for in vivo protection different from that implicated in in vitro neutralization. Administration of one MoAb (55) led to a retarded neurological disease. Mice receiving lower quantities of other protective MoAbs did not display such disease. These results are discussed in relationship to immunization and protection.