title: 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.
abstract: Merozoite surface protein-1 (MSP-1) is a major candidate in the development of a vaccine against malaria. Immunisation with a recombinant fusion protein containing the two Plasmodium yoelii MSP-1 C-terminal epidermal growth factor-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(19) may be crucial in determining the potential of this protein as a vaccine. Representative sequence variants from a number of distinct P. yoelii isolates were expressed in Escherichia coli and the resulting recombinant proteins were screened for binding to a panel of monoclonal antibodies (Mabs) capable of suppressing a P. yoelii YM challenge infection in passive immunisation experiments. The sequence polymorphisms affected the binding of the antibodies to the recombinant proteins. None of the Mabs recognised MSP-1(19) of P. yoelii yoelii 2CL or 33X or P. yoelii nigeriensis N67. The epitopes recognised by the Mabs were further distinguished by their reactivity with the other fusion proteins. The extent of sequence variation in MSP-1(19) among the isolates was extensive, with differences 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 also cloned and the deduced amino acid sequence compared with that in other species.
authors.affiliation: Division of Parasitology, National Institute for Medical Research, London, UK.
authors.forename: P A
authors.initials: PA
authors.lastname: Benjamin
authors.forename: I T
authors.initials: IT
authors.lastname: Ling
authors.forename: G
authors.initials: G
authors.lastname: Clottey
authors.forename: L M
authors.initials: LM
authors.lastname: Valero
authors.forename: S A
authors.initials: SA
authors.lastname: Ogun
authors.forename: S L
authors.initials: SL
authors.lastname: Fleck
authors.forename: D
authors.initials: D
authors.lastname: Walliker
authors.forename: W D
authors.initials: WD
authors.lastname: Morgan
authors.forename: B
authors.initials: B
authors.lastname: Birdsall
authors.forename: J
authors.initials: J
authors.lastname: Feeney
authors.forename: A A
authors.initials: AA
authors.lastname: Holder
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000913:Antibodies, Protozoan / Q000276:immunology; D015153:Blotting, Western; D003001:Cloning, Molecular; D004815:Epidermal Growth Factor / Q000235:genetics; D014644:Genetic Variation; D008288:Malaria / Q000469:parasitology*; D020066:Merozoite Surface Protein 1 / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D010961:Plasmodium / Q000235:genetics / Q000302:isolation & purification; D010967:Plasmodium yoelii / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification; D051381:Rats; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology; D017422:Sequence Analysis, DNA
chemical_list: D000911:Antibodies, Monoclonal; D000913:Antibodies, Protozoan; D020066:Merozoite Surface Protein 1; D011994:Recombinant Proteins; D004815:Epidermal Growth Factor