Monoclonal anti-idiotypic antibodies mimicking the immunodominant epitope of influenza virus haemagglutinin elicit biologically significant immune responses.

The MAb IIB4 recognizes an immunodominant epitope on influenza virus haemagglutinin (HA) which is shared by different strains of the human subtype H3. This epitope includes amino acids 198, 199 and 201, as determined by selection of IIB4 escape mutants, and is involved in haemagglutination-inhibition (HI) and virus-neutralization (VN). We have developed anti-idiotypic MAbs (Ab2) that mimic the IIB4 epitope. Two Ab2, 78 and 464, completely inhibited binding of MAb IIB4 to the virus. Nucleotide sequences of VL- and VH-encoding regions were determined for IIB4 and both Ab2. VH of IIB4 and 78 belong to the same IgG family (VII) and show high nucleotide identity (89%). Conversely, VH and VL sequences of both internal image-bearing Ab2 revealed lower degrees of identity (61 and 50%, respectively). Ab2 were used for syngeneic immunization to elicit polyclonal Ab3 responses. Like Ab1, Ab3 immunoprecipitated viral HA and displayed HI and VN activity. The different VN activity of anti-78 and anti-464 in vitro correlated with the affinities of their corresponding Ab2 to IIB4. In vivo immunization with either Ab2 protected 15-37% of mice against lethal influenza infection or delayed dying. In contrast to VN activity of Ab3 in vitro, there was no significant difference between the protection of mice induced by Ab2 78 and 464. We demonstrate, for the influenza model, that active immunization with a single influenza virus HA epitope in the form of its internal image leads to partial protection in vivo.