Three
subunit vaccines based on the major repeat, (QGPGAP)n, and flanking regions of the Plasmodium yoelii circumsporozoite
protein were designed, produced, and tested. All were immunogenic, but none gave consistent protection against a 40-200 sporozoite challenge. To demonstrate that
antibodies to P. yoelii CS
protein could provide protection we established a passive transfer model. Passive transfer of
NYS1, an
IgG3 MAb against the P. yoelii CS
protein, protected 100% of mice against challenge with 5000 P. yoelii sporozoites. Binding of
NYS1 to sporozoites was inhibited by incubation with (QGPGAP)2, indicating that the
epitope on sporozoites recognized by this MAb was included within this
peptide. The levels of
antibodies to (QGPGAP)2 by ELISA, and to sporozoites by IFAT and CS precipitation reaction were similar in sera from mice that received
NYS1 in passive transfer and were protected against challenge with 5000 sporozoites, and from mice that had been immunized with
subunit vaccines containing QGPGAP but were not protected against challenge with 40-200 sporozoites. To determine if antibody avidity, not the absolute concentration, could explain the striking differences in protection, we established a
thiocyanate elution assay. The results suggest that
NYS1, the protective MAb, has a lower avidity for (QGPGAP)2 and for sporozoites than do the
vaccine-induced
antibodies. The data clearly demonstrate that
antibodies to the CS
protein can protect against intense sporozoite
infection. Improved understanding of the differences between protective MAbs and non-protective polyclonal
antibodies will be important in the further development of
malaria vaccines.