Clinical and Serologic Response of Man to Immunization with Attenuated Dengue and Yellow Fever Viruses

Abstract

Summary: Human volunteers inoculated with mouse-adapted type II dengue virus (New Guinea B strain) responded with mild clinical reactions indicating that the virus had become attenuated in a manner comparable to that previously shown for type I virus (Hawaii strain). The most significant and consistent sign was a maculopapular rash. In 10 of 11 volunteers, a single dose of attenuated type II dengue virus induced formation of homologous neutralizing antibody. When attenuated type II virus was given in combination with yellow fever vaccine or with yellow fever vaccine and attenuated type I dengue virus, the resulting antibody response was predominantly to type II virus, indicating suppression of the other antigens presumably as a result of interference. Not enough volunteers were available to vary the relative concentration of the components in the mixtures. Attenuated type II dengue virus or combined vaccine was inadvertently administered to 4 men who had been immunized against yellow fever 7–7 ½ years previously. These men gave an anamnestic immune response characterized by rapid production of complement-fixing (3 men only) and neutralizing antibodies of comparable potency against types I and II dengue and yellow fever viruses. The findings suggest consecutive immunization with yellow fever and an attenuated, related viral antigen as a possible method of broad-spectrum prophylaxis.