PROTECTIVE EFFICACY AGAINST MALARIA OF A COMBINATION SPOROZOITE AND ERYTHROCYTIC STAGE VACCINE

Most malariologists believe that optimal malaria vaccines will induce protective immune responses against different stages of the parasite's life cycle. A multiple antigen peptide (MAP) vaccine based on the Pla smodium yoelii circumsporozoite protein (PyCSP) protects mice against sporozoite challenge by inducing antibodies that prevent sporozoites f rom invading hepatocytes. A purified recombinant protein vaccine based on the P. yoelii merozoite surface protein-1 (PyMSP-1) protects mice against challenge with infected erythrocytes, presumably by inducing a ntibodies against the erythrocytic stage of the parasite. We now repor t studies designed to determine if the PyMSP-1 vaccine protects agains t challenge with sporozoites, the stage encountered in the field, and if immunization with a combination of the PyCSP and PyMSP-1 vaccines p rovides additive or synergistic protection against sporozoite challeng e. In two experiments, using TiterMax(R) or Ribi R-700 as adjuvant, 3 of 19 mice immunized with the PyMSP-1 vaccine were completely protecte d against sporozoite challenge. The remaining mice had significantly d elayed onset and lower levels of peak parasitemia than did control mic e (11.1 +/- 2.8% vs. 36.7 +/- 1.6% in experiment #2, P < 0.01). Immuni zation with the combination vaccine reduced by approximately 50% the l evel of antibodies induced to PyCSP and PyMSP-1, as compared to that i nduced by the individual components. However, in two experiments, ther e was evidence of additive protection. Six of 19 (31.6%) immunized wit h the PyCSP vaccine, 3 of 19 (15.8%) immunized with the PyMSP-1 vaccin e, and 10 of 19 (52.6%) immunized with the combination were completely protected against sporozoite challenge. This modest increase in prote ction in the combination group may be a reflection of additive anti-Py CSP and anti-PyMSP-1 immunity, since mice in the combination group had diminished levels of antibodies to each components. These studies ind icate that considerable work may be required to optimize the construct ion, delivery, and assessment of multi-stage malaria vaccines.