Induction of immunity against Schistosoma mansoni by drug (Ro11-3128)-terminated infections: analysis of surface antigen recognition.

As with 20 krad-irradiated infections in mice, the present study shows that the immunity induced by Ro11-3128 termination of unattenuated infections at the skin stage is species specific, not operating against S. japonicum. Treatment with the drug Ro15-5458, also effective at the skin stage, however, resulted in significantly lower levels of resistance than Ro11-3128. Sera from mice immunized by infection plus Ro11-3128 treatment on days 1 or 2 (Ro11S) coprecipitated essentially the same pattern of 125I-labelled surface antigens as the 20 krad vaccine serum (VMS), viz. Mr 38,000, 32,000, 23,000 and 15,000. However, recognition by Ro11S was markedly stronger. Sera from the infected and Ro15-5458-treated mice (Ro15S) failed to recognize the Mr 23,000 antigen and produced a weaker response than Ro11S or VMS against the Mr 38,000 or 32,000 antigens but a comparable response to VMS against the Mr 15,000 antigen. Ro11S and VMS also recognized the Mr 16,000 surface antigen seen by Western blotting but its recognition by Ro15S was weaker. Compared with sera from animals treated at the skin stage, sera from animals treated at the lung stage (day + 6) showed weaker recognition of the Mr 32,000 and 15,000 antigens and no recognition of the Mr 23,000 antigen. In contrast, sera from mice treated at 15 days recognized both the Mr 32,000 and 23,000 antigens but not the Mr 15,000 antigen. Mice treated at these times show progressively less immunity than at the skin stage. Infected but untreated animals only showed significant recognition of the Mr 32,000 antigen. Thus compared with infections treated with Ro11-3128 on days 1 or 2, treatment at later times or with the drug Ro15-5458 resulted in selective and differential absence or diminution of response against either the Mr 38,000, 32,000, 23,000, 16,000 or 15,000 antigens. In vitro, Ro11-3128, in contrast to Ro15-5458, caused multiple vesicle formation at the surface of skin stage schistosomula but this was progressively less pronounced with lung and liver stage worms. The vesicles were shown to express surface membrane antigens but were apparently not derived from the existing outer leaflet of the surface membrane. It is suggested that this altered antigen expression might explain the optimum immunity induced.