Antigenic and sequence diversity at the C-terminus of the merozoite surface protein-1 from rodent malaria isolates, and the binding of protective monoclonal antibodies

Merozoite surface protein-1 (MSP-1) is a major candidate in the development of a vaccine against malaria, Immunisation with a recombinant fusion prote in containing the two Plasmodium yoelii MSP-1 C-terminal epidermal growth f actor-like domains (MSP-1(19)) can protect mice against homologous but not heterologous challenge, and therefore, antigenic differences resulting from sequence diversity in MSP-1,, may be crucial in determining the potential of this protein as a vaccine. Representative sequence variants from a numbe r of distinct P. yoelii isolates were expressed in Escherichia coil and the resulting recombinant proteins were screened for binding to a panel of mon oclonal antibodies (Mabs) capable of suppressing a P. yoelii YM challenge i nfection in passive immunisation experiments. The sequence polymorphisms af fected the binding of the antibodies to the recombinant proteins. None of t he Mabs recognised MSP-1(19) of P. yoelii yoelii 2CL or 33X or P, yoelii ni geriensis N67. The epitopes recognised by the Mabs were further distinguish ed by their reactivity with the other fusion proteins. The extent of sequen ce variation in MSP-1(19) among the isolates was extensive, with difference s detected at 35 out of the 96 positions compared. Using the 3-dimensional structure of the Plasmodium falciparum MSP-1(19) as a model, the locations of the amino acid substitutions that may affect Mab binding were identified . The DNA sequence of MSP-1(19) from two Plasmodium vinckei isolates was al so cloned and the deduced amino acid sequence compared with that in other s pecies. (C) 1999 Elsevier Science B.V. All rights reserved.