Dose-response relationship after immunization of volunteers with a new, surface-antigen-adsorbed influenza virus vaccine.

Volunteers (15 per group) were given inoculations of various doses (5-400 international units [IU]) of surface-antigen-adsorbed influenza virus A/Port Chalmers/73 vaccine; this vaccine was prepared from purified virus hemagglutinin and neuraminidase antigens and adsorbed to alhydrogel. The titers of hemagglutination-inhibiting (HAI) and neuraminidase-inhibiting antibodies in serum after immunization showed a clear dose-response relationship. Thus, for volunteers given 400, 100, 25, or 5.0 IU of vaccine, the titers of HAI antibody in serum increased 174-, 32-, 12-, and eightfold, respectively. A similar dose response was observed for production of local neutralizing antibody. Immunization with A/Port Chalmers/73 virus vaccine also induced serum HAI antibody to influenza viruses A/Scotland/74, A/England/72, and A/Hong Kong/68; the increase in titers of antibody to these viruses corresponded directly to the degree of cross-reactivity between the virus tested and the vaccine virus. Four weeks after immunization, all volunteers were challenged with attenuated WRL-105 influenza virus. Evidence of viral infection was found in one, two, and two volunteers in each group of 15 subjects previously immunized with 400, 100, and 25 IU of vaccine, respectively; in six of the 15 volunteers given 5.0 IU of vaccine; and in 10 of 15 control subjects. The results suggest that equivalent immunity was induced in volunteers given greater than or equal to 25 IU of vaccine.