ANTIGENIC DRIFT OF NONENCAPSULATED HAEMOPHILUS-INFLUENZAE MAJOR OUTER-MEMBRANE PROTEIN P2 IN PATIENTS WITH CHRONIC-BRONCHITIS IS CAUSED BY POINT MUTATIONS

The sequence of the gene encoding major outer membrane protein (MOMP) P2 of antigenic variants of nonencapsulated Haemophilus influenzae isolated from persistently infected chronic bronchitis patients was analysed. Antigenic drift was shown to result from single base changes in the P2 gene, all generating amino acid changes in the surface-exposed loops of MOMP P2, predominantly in loop 6. Similar single base changes were observed in H. influenzae persistently present in a subcutaneous cage implanted in rabbits, as well as in a spontaneous ii. influenzae mutant that had survived MOMP P2 specific monoclonal-antibody-dependent bactericidal killing in vitro. We hypothesize that accumulation of point mutations under the selection pressure of immunity is a mechanism of antigenic drift of a surface-exposed protein during persistent H. influenzae infection.