Effect of Adjuvants on Vaccination of Human Beings Against Influenza. ∗

Immunization of human subjects against influenza Types A and B with adequate vaccines prepared from infected allantoic fluids of the chick have afforded protection against the natural or experimental disease for a limited period of time. In most instances the duration of the immune state has been found to correlate roughly with the height of the serum antibody level in the vaccinated individuals. 1 The titer reaches its peak about 2 weeks after vaccination and decreases thereafter more or less rapidly until the pre-vaccination level is reached, usually 4-12 months after immunization. This time relationship seems to hold regardless of the kind of vaccine used. 2 Therefore, the problem of protection against influenza lies not so much in the preparation and use of vaccines producing maximal antibody response in men, but rather in the maintenance of adequate antibody levels for a prolonged period of time.

The studies of Freund and his co-workers 3 have shown that the addition of certain adjuvants (lanolin-like substances and killed tubercle bacilli in paraffin oil) increase and prolong antibody production to various antigens in rabbits and guinea pigs. Friedewald 4 applied these findings to the immunization of animals against influenza. Recently Salk 5 reported the adjuvant effect of calcium phosphate on vaccination against influenza in mice. A study was begun in this laboratory in June, 1944, using influenza vaccines combined with adjuvants, except for the tubercle bacilli, in human beings and a brief summary of the results up to the sixth month is presented below.

Centrifugally concentrated influenza virus vaccine of Types A and B prepared according to the method of Stanley, 6 formed the stock material.† One part of this stock vaccine was emulsified in one part of Falba‡ to which 4 parts of mineral oil§ were added with constant agitation.