Heterologous immunity in rodent malaria: comparison of the degree of cross-immunity generated by vaccination with that produced by exposure to live infection.

The degree of heterologous immunity occurring between the different rodent malarias was examined. Mice immunized with a killed vaccine consisting of formalin-fixed blood-stage parasites mixed with saponin, were challenged with homologous or heterologous parasites and the degree of protection assessed by monitoring the number of survivors and the duration and severity of parasitaemia. The results indicated that vaccination conferred strong cross-protection between two different Plasmodium yoelii lines and also some cross-protection between different species. The most significant inter-species cross-immunity was in P. berghei-vaccinated mice challenged with P. yoelii (33% survival rate) and in P. vinckei-vaccinated mice challenged with P. chabaudi (50% survival rate). The protection operated only in one direction since mice vaccinated against P. yoelii or P. chabaudi were fully susceptible to P. berghei and P. vinckei respectively, although extension of the survival time did occur in both cases. Significantly greater levels of homologous and heterologous immunity occurred in vaccinated mice which had cleared a primary homologous infection. All recovered animals were fully resistant to homologous secondary challenges. P. berghei-recovered mice had complete resistance to a secondary P. yoelii challenge, with partial resistance also to P. vinckei and P. chabaudi: P. vinckei-recovered mice were completely resistant to P. chabaudi challenge and showed partial resistance to P. berghei (50% survival rate). Conversely, no reduction in mortality occurred in P. chabaudi-recovered mice challenged with any heterologous parasite. Plasmodium yoelii-recovered animals were fully susceptible to P. vinckei but showed some resistance to P. berghei and P. chabaudi (33 and 17% survival respectively). Many lesser instances of cross-resistance were observed in the present study and are discussed in the text but they were not sufficiently powerful to reduce mortality. The present study provides the first reported comprehensive investigation on cross-resistance in rodent malarias generated by a killed vaccine. In addition this is the only complete cross-resistance study available which has concentrated exclusively upon highly lethal strains of each parasite species. Taken with the rechallenge experiments, the results extend, and to a certain point confirm, previous observations on cross-immunity in the rodent malarias. However, several of the present results conflict with previous reports and these are discussed in relation to the relevant literature.