Effect of Neuraminidase on Antibody Combining Unit (ACU) Titers of Human Sera Determined by Drescher's Photometric Procedure 1

Drescher-photometric technique, which differentiates between inhibition of hemagglutination strain specific antibody from that caused by nonspecific inhibition or cross reacting antibodies, has been used in our laboratory to validate the specificity of antibody patterns found in human serum by conventional HI tests (1). On the basis of the age distribution of antibodies to prototype strains, the data have been interpreted to indicate that mankind has experienced in succession past periods of prevalence of swine, Hong Kong, Asian and Equine-2 like viruses, respectively, during the outbreaks of 1918-19, 1900 and 1889-90 and on at least 2 occasions during the period 1874-1888 (2–6).

At the time that these studies were being carried out, it had not been recognized that in special circumstances antibody mediated inhibition of hemagglutination could be effected solely by antineuraminidase antibodies presumably by causing steric hindrance with viral hemagglutinin (7). That finding raised the question whether the antibody patterns heretofore described might not be related to similarities of enzymes rather than to similarities of hemagglutinins present in the strains of former periods of prevalence. This alternate explanation seemed unlikely because in our experience HI titers of human serum caused by antineuraminidase antibodies were demonstratable only by use of erythrocytes of selected chickens or by addition of anti-human IgG to the reaction mixture, conditions that were not required for the demonstration of the antibody patterns (8). Moreover, the frequency and the height of titers observed at the peak of the antibody patterns were considerably greater than was found when measuring antineuraminidase antibody by HI under the best of conditions (12). However, to obtain direct evidence on the question whether the antibody patterns of human sera are oriented to viral hemagglutinin rather than to viral enzyme, a set of convalescent specimens were tested by Drescher's technique using a homologous natural virus and a recombinant containing the homologous hemagglutinin but a heterologous enzyme.