Antibody response in man to influenza virus neuraminidase following influenza.

Genetic recombination of influenza viruses of different subtype may result in segregation of hemagglutinin and neuraminidase in antigenically hybrid viruses [E. D. Kilbourne et al., in M. Pollard (ed.), Perspectives in Virology, vol. 5, p. 87, Academic Press, Inc., N.Y., 1967; and W. G. Laver and E. D. Kilbourne, Virology 30:493, 1966]. The selective use of such antigenic hybrids in serological reactions permits the independent measurement of antibodies to the envelope proteins of the virion, i.e., hemagglutinin, and neuraminidase (E. D. Kilbourne et al., J. Virol. 2:281, 1968). In conventional hemagglutinationinhibition (HI) reactions, antibody to the hemagglutinin is titrated and is considered a measure of response to immunization or infection. Recently, by the use of recombinant hybrids and isolated viral neuraminidase, it has been shown that experimental infection of mice produces large amounts of antibody to the neuraminidase of the infecting influenza virus (J. L. Schulman et al., J. Virol., in press). In the present paper, we present evidence that similar increase in antineuraminidase occurs in man during and after natural infection. Serum was obtained from six adult patients during the acute phase of illness and 14 to 23 days later. In the fatal case 1012, the bleeding interval was only 3 days. HI tests were conducted as described previously after serum inhibitors were inactivated by heat and periodate (S. C. Wong and E. D. Kilbourne, J. Exptl. Med. 113: 95, 1961). Neuraminidase (enzyme) -inhibition tests were conducted as described previously (E. D. Kilbourne et al., J. Virol. 2:281, 1968), employing a virus [X-7(F1)] with Ao hemagglutinin and A2 (E) enzyme. Six viruses were used in HI tests: A.2/Cornell/1001 /67, A2/RI/5/57 ("+" and "-" variants, P. W. Choppin and I. Tamm, J. Exptl. Med. 112:895, 1960), A/equine/I /56, and two recombinants, X-9 and X-15 (see footnote to Table 1). Recombinant X-15 is uniquely susceptible to in vitro inhibition with antibody to A2 neuraminidase (anti-E), so that its inhibition in HI tests is a specific measure of A2 neuraminidase antibody (E. D. Kilbourne, Science 160:74, 1968). Because the recombinants used to measure neuraminidase antibody [X-15 and X-7(F1)] had derived their enzyme component from A2/RI/