A FAIRLY CONSERVED EPITOPE ON THE HEMAGGLUTININ OF INFLUENZA-A (H3N2)VIRUS WITH VARIABLE ACCESSIBILITY TO NEUTRALIZING ANTIBODY

A monoclonal antibody LMBH5 was derived from mice which had been immun ized with A/Victoria/3/75 (H3N2)-type recombinant, secreted hemaggluti nin (HA), and were subsequently challenged with a potentially lethal d ose of X31 [A/Aichil/2/68 (H3N2) x A/PR/8/34 (H1N1)] virus. LMBH5 reac ted strongly with the native and low-pH-induced conformations of the H A of A/Aichi (X31 strain) and A/Victoria (X47 strain), but very weakly with the native structure of the HA of A/Philippines/2/82 (X79 strain ) and not at all with the HA of A/Guizhou/54/89 H3 (NIB25 strain). How ever, the acid-induced conformations of the latter two viruses were re cognized by LMBH5. The antibody prevented infection of MDCK cells with X31 and X47, whereas X79 virus was partially neutralized by LMBH5. X3 1 monoclonal escape variants had single amino acid substitutions (Ser 227 --> Pro) near the interface. The data obtained suggest that the ne utralizing LMBH5 reacts with a fairly conserved epitope of influenza A (H3N2) virus, which as a result of antigenic drift becomes inaccessib le in the native state of the HA. (C) 1995 Academic Press, Inc.