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 immunized with A/Victoria/3/75 (H3N2)-type recombinant, secreted hemagglutinin (HA), and were subsequently challenged with a potentially lethal dose of X31 [A/Aichi/2/68 (H3N2) x A/PR/8/34 (H1N1)] virus. LMBH5 reacted strongly with the native and low-pH-induced conformations of the HA 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). However, the acid-induced conformations of the latter two viruses were recognized by LMBH5. The antibody prevented infection of MDCK cells with X31 and X47, whereas X79 virus was partially neutralized by LMBH5. X31 monoclonal escape variants had single amino acid substitutions (Ser 227-->Pro) near the interface. The data obtained suggest that the neutralizing LMBH5 reacts with a fairly conserved epitope of influenza A (H3N2) virus, which as a result of antigenic drift becomes inaccessible in the native state of the HA.
Vanlandschoot
P
P
Laboratory of Molecular Biology, Gent University, Belgium.
Beirnaert
E
E
Dewilde
S
S
Saelens
X
X
Bestebroer
T
T
De Jong
J
J
Jou
W M
WM
Fiers
W
W
D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism; D000914:Antibodies, Viral / Q000378:metabolism; D000939:Epitopes / Q000032:analysis* / Q000737:chemistry; D005814:Genes, Viral / Q000235:genetics; D006386:Hemagglutination Tests; D006389:Hemagglutinins, Viral / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D053122:Influenza A Virus, H3N2 Subtype; D009980:Influenza A virus / Q000276:immunology*; D051379:Mice; D009154:Mutation; D009500:Neutralization Tests; D011487:Protein Conformation; D013045:Species Specificity; D014357:Trypsin; D015678:Viral Structural Proteins / Q000235:genetics
D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D000939:Epitopes; D006389:Hemagglutinins, Viral; D015678:Viral Structural Proteins; D014357:Trypsin