Immunization against parasites: bridging the gap between attenuated and non-living vaccines

While great progress has been made in the last decade in defining parasite antigens which are targets of host protective responses, only limited success has been achieved in the use of these molecules as effective vaccines. A consistent problem is the failure of the candidate immunogens to induce levels of protection comparable to those obtained with attenuated vaccines against the same organisms. One explanation is that the purified or recombinant molecules employed have not been presented in a form or route which induces the correct T cell or cytokine response necessary for protection. As summarized in this overview, optimal immunization with attenuated vaccines is associated with characteristic patterns of T cell subset and cytokine induction and in at least several examples has been shown to be altered by exogenous cytokine. We hypothesize that cytokine manipulation may offer a useful strategy for improving the action of existing nonliving vaccines. The gap in efficacy between attenuated and dead vaccines could also be bridged by the use of live recombinant vaccine vectors. We have previously reported that paramyosin admixed with BCG can induce partial protection against Schistosoma mansoni in mice. Our preliminary results in the construction and testing of a recombinant BCG vector incorporating schistosome paramyosin are described.