A direct proportion exists between the concentration of epidemic influenza virus used for intraperitoneal immunization of mice and the degree of immunity to intranasal infection which develops. Mice vaccinated with virus of a given strength resist infection with virus of the same concentration but not more. An irreducible minimum exists since mice vaccinated with less than ten intranasal lethal doses do not develop sufficient immunity to overcome intranasal infection with virus of the same strength. The fact that there exists a limiting threshold for the degree of immunity which a certain strength of virus will induce indicates that the virus does not multiply after intraperitoneal inoculations.
In ferrets a state of partial immunity is induced as a result of subcutaneous vaccination with active influenza virus. Vaccination with doses containing 100 or more intranasal infectious units is required for the production of circulating antibodies, protection of the animals from pulmonary involvement, and modification of the severity of the disease. On the other hand, intranasal inoculation with one infectious unit results in a firm, immediate immunity, although the duration of immunity may bear a relation to the severity of the original infection and consequently to the size of the infecting dose.
Ferrets in a state of partial immunity resulting from subcutaneous vaccination, or from the waning of a firm immunity following infection, respond to intranasal inoculation of influenza virus with an accelerated production of neutralizing antibodies. The antibody titer under these conditions reaches a much higher level than occurs following a primary infection. Fully immune animals, however, show no further antibody response to a second inoculation.