Human antibodies against Plasmodium falciparum liver-stage antigen 3 cross-react with Plasmodium yoelii preerythrocytic-stage epitopes and inhibit sporozoite invasion in vitro and in vivo

The Plasmodium falciparum liver-stage antigen 3 (LSA3), a recently identifi ed preerythrocytic antigen, induces protection against malaria in chimpanze es. Using antibodies from individuals with hyperimmunity to malaria affinit y purified on recombinant or synthetic polypeptides of LSA3, we identified four non-crossreactive B-cell epitopes in Plasmodium yoelii preerythrocytic stages. On sporozoites the P. yoelii protein detected has a molecular mass similar to that of LSA3. T-cell epitopes cross-reacting with P. yoelii wer e also demonstrated using peripheral blood lymphocytes from LSA3-immunized chimpanzees. In contrast, no cross-reactive epitopes were found in Plasmodi um berghei. LSA3-specific human antibodies exerted up to 100% inhibition of in vitro invasion of P. yoelii sporozoites into mouse hepatocytes. This st rong in vitro activity was reproduced in vivo by passive transfer of LSA3 a ntibodies. These results indicate that the homologous epitopes may be biolo gically functional and suggest that P. yoelii could be used as a model to a ssess the antisporozoite activity of anti-LSA3 antibodies.