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Experiments on Vaccination of Human Beings against Epidemic Influenza¹

From the Department of Pediatrics, School of Medicine, University of Pennsylvania, The Children's Hospital of Philadelphia, and the Medical-Research Division of Sharp and Dohme, Inc., Glenolden, Pennsylvania

Abstract

Studies have been reported on the vaccination of human beings against influenza A and B in regard to (1) the effect of single and multiple doses of vaccine; (2) comparison between allantoic-fluid vaccines and concentrates prepared therefrom; (3) the persistence of elevated antibody levels; and (4) the effects of adjuvants on the antibody response.

(1) There was no added effect on repeated intramuscular injection of vaccine, i.e., one injection of allantoic-fluid vaccine gave as good a geometric mean antibody response as three injections at weekly intervals. Inhalation of vaccine in addition to one intramuscular injection, likewise, failed to increase the antibody response.

(2) Concentrated vaccines prepared by precipitation with protamine gave higher geometric mean antibody levels than allantoic-fluid vaccines. Three ml of allantoic fluid, in turn, resulted in higher titers than 1 ml doses. Results, reported elsewhere, of experiments on infection of human beings with influenza virus suggested that subjects with antibody titers of greater than 1:128 were "probably immune," those with lower levels, "potentially susceptible" to the disease. Classification of the subjects in the various groups according to this suggestion showed little difference in protection afforded by the concentrated preparation and the 3 ml dose of allantoic-fluid vaccine.

(3) Although the geometric mean antibody levels 2 weeks after vaccination were increasingly higher with the increase in the dose of antigen injected, this difference tended to become less obvious in 3 months, and by the end of 6 months all groups were practically alike.

(4) Protamine did not seem to exert an adjuvant effect. Emulsion of the vaccine in Falba and mineral oil, on the other hand, was highly effective in increasing and prolonging the antibody response. Practically all subjects in this series passed the "threshold antibody level" of 1:128 within 2 to 3 months, whereas in the controls injected with slightly larger amounts of vaccine in saline solution, only 70 per cent ever reached the "protective level" in 2 weeks at the time of maximal response. One year after vaccination with the adjuvants the geometric mean antibody levels both for influenza A and B were still above the maxima obtained in the control series. After 18 months, this was still true for the influenza B reactions, but no more for the influenza A titer. However, in this case the geometric mean was still 3 times higher than the pre-vaccination level. The titers in the control series receiving vaccine in saline solution had returned to the pre-vaccination level in the case of influenza A within one year, whereas the influenza B titers were still above the initial level at the end of 18 months, but 70 per cent of the subjects had titers below 1:128. These data suggest that protection may be afforded for at least 2 winters following vaccination with mineral oil as adjuvant. The technic requires further study to decrease the incidence of abscess formation which was noted in 2 out of 80 subjects or of 120 sites of injection.

Footnotes

¹ Part of the work described in this paper was done under contract, recommended by the Committee on Medical Research, between the Office of Scientific Research and Development and the Children's Hospital of Philadelphia.