Antibody Response in Volunteers to Adenovirus Vaccine and Correlation of Antibody with Immunity

Abstract

Formalin-killed bivalent and monovalent types 4 and 7 adenovirus vaccines prepared under commercial conditions were assayed for homologous and heterologous neutralizing antibody response in a study with 267 volunteers. The vaccine employed in the studies induced a neutralizing antibody titer of 1:1 in guinea pigs against type 4 virus and 1:4 against type 7 virus when assayed by the standard test method employed. Dilution of bivalent vaccine more than 1:2 for type 4 component and around 1:27 for type 7 component significantly reduced the antibody response to the vaccine. The type 7 component induced a high level of neutralizing antibody against types 7, 7a, and 3 with essentially no antibody against types 4 or 14, and the type 4 component induced significant antibody against type 4 virus only. Bivalent vaccine given in 1 ml amount by jet gun or in 0.1 ml volume intradermally induced as much antibody as the 1 ml dose given intramuscularly. The antibody stimulated against bivalent vaccine was reduced by no more than 50% during a 10 month period post-vaccination and the response to a booster dose of vaccine given at that time elevated the titer only slightly above that achieved initially. There was a close correlation between the occurrence of serum neutralizing antibody and failure to develop adenovirus-caused respiratory illness among recruits in basic training. The level of antibody associated with immunity appeared in most cases not to exceed a titer of 1:1 when assayed by the standard method employed in this laboratory. The occurrence of type 3 antibody in persons whose sera were devoid of type 7 antibody, appeared to afford some protection against type 7 virus disease though this was not always the case. The significance of the finding in relation to the application and use of adenovirus vaccine is discussed.