Minimal variation in the transmission-blocking vaccine candidate Pfs48/45 of the human malaria parasite Plasmodium falciparum

• Published in: Molecular and biochemical parasitology 1995-01, Vol.69 (1), p.115-118
• Main Authors: Kocken, C H, Milek, R L, Lensen, T H, Kaslow, D C, Schoenmakers, J G, Konings, R N
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Animals; Base Sequence; Epitope Mapping; Genetic Variation; Membrane Glycoproteins - genetics; Membrane Glycoproteins - immunology; Molecular Sequence Data; Plasmodium falciparum; Plasmodium falciparum - genetics; Plasmodium falciparum - immunology; Polymorphism, Single-Stranded Conformational; Protozoan Proteins - genetics; Protozoan Proteins - immunology; Protozoan Vaccines
• ISSN: 0166-6851
• DOI: 10.1016/0166-6851(94)00193-Q

Recently we reported the isolation and characterization of the Plasmodium falciparum gene Pfs48/45 (strain NF54) that codes for a gametocyte/gamete-specific surface antigen, which is an important target antigen for transmission-blocking immunity. To assess the suitability of this antigen for incorporation in a transmission-blocking subunit vaccine, it is important to know its antigenic diversity as it occurs in the field. Therefore we analyzed the nucleotide sequences of the Pfs48/45 genes in 7 in vitro cultivated P. falciparum strains collected from various geographic areas, i.e., Brazil (7G8), Liberia (LE5, LF4), Ghana (GH1), Honduras (HB3), Malaysia (CAMP), and Indochina (Dd2), and compared these with that of NF54, thought to be of African origin. Immunological studies with Pfs48/45 specific monoclonal antibodies have shown that antigen Pfs48/45 contains at least 5 B-cell epitopes: I, IIa or IIc, IIb, III and IV, of which the first 4 are tertiary structure dependent. The only polymorphic epitopes identified thus far are IIa and IIc, which behave as though they are mutually exclusive. Because epitope IIa is absent from gene Pfs48/45 of strain NF54, but present in that of 7G8, and conversely epitope IIc is absent from 7G8 but present in NF54 (Pieter Beckers and Ton Lensen, personal communication), the entire nucleotide sequence of the coding region of the intronless gene Pfs48/45 of 7G8 was established. First, the coding region (1347 base pairs) was amplified with the polymerase chain reaction (PCR) using primers previously described.