Relative Merits of Aqueous and Adjuvant Influenza Vaccines When Used in a Two-Dose Schedule

Abstract

A RECOMMENDATION that persons of all ages be vaccinated against influenza by giving them two doses of vaccine was first made in 1957 by the Commission on Influenza, Armed Forces Epidemiological Board. This recommendation stemmed from the demonstration that the primary antibody response of man to influenza virus vaccines seemed inadequate. For example, infants and children respond irregularly and poorly to a single dose of influenza virus vaccine (1-5). Young adults and persons over 30 likewise fail to develop uniformly high antibody levels when vaccinated once with those strains of influenza virus which they have not previously encountered by infection (2,6-8). Fortunately, it had been clearly established that vaccination was capable of laying the foundation for a booster response in children and adults (3,4). Hence, in order to meet the emergency when the antigenically novel Asian strains appeared in 1957, the recommendation of a two-dose schedule of vaccination could be made with confidence. Since 1957 a schedule of two doses of influenza virus vaccine for protection against influenza ha,s been adopted by the military and recommended to segments of the civilian population (9,10). Meanwhile, general interest has accumulated in the use of those adjuvant influenza virus vaccines emulsified in mineral oil that have been under development since 1951 by the Commission on Influenza. Consequently, it seems timely to report on the results of a series of investigations undertaken to compare antibody responsels of humans given either two doses of aqueous vaccine, two doses of adjuvant vaccine, or one dose of vaccine of one kind followed by a second dose of the other kind. The findings indicate that mineral oil adjuvant vaccine, when used as one or both inoculations in a two-dose schedule, is remarkably effective for stimulating high, broad, uniform, and persistent antibody levels against prototype strains of influenza A viruses, regardless of prior natural exposures. Furthermore, when two doses of adjuvant vaccine are given within an interval of 2 to 3 months, a The authors are with the virus laboratory, department of epidemiology, University of Michigan School of Public Health, Ann Arbor. This investigation was conducted under the auspices of the Commission on Influenza, Armed Forces Epidemiological Board, and was supported by the Office of the Surgeon General, U.S. Army, Washington, D.C.