Conserved and Variant Epitopes of Target Antigens of Transmission-Blocking Antibodies among Isolates of Plasmodium falciparum from Malaysia

A Plant-Produced Pfs230 Vaccine Candidate Blocks Transmission of Plasmodium falciparum

“…In the 1980s, incidents of serum-mediated TB activity were reported in individuals infected with Plasmodium vivax (25) and serum samples collected during field studies contained antibodies against the gametocyte surface proteins Pfs230 and Pfs48/45 (12,15,17,27,29,33,36). Additionally, Graves et al (15) and Healer et al (17) showed a positive correlation between the abilities of sera to immunoprecipitate 125 I-labeled Pfs230 and to block P. falciparum transmission in a standard membrane feeding assay (SMFA).…”

Minimal variation in the transmission-blocking vaccine candidate Pfs4845 of the human malaria parasite Plasmodium falciparum

“…Taken together, the results of the immunological [10][11][12] and structural studies (Fig. 1A) suggest that the amino acid residue at position 254 in Pfs48/45 dictates whether antigen Pfs48/45 will bind to a monoclonal antibody that is specific for epitope Ila or epitope lie.…”

“…Dd2 has a T-A transversion at position 911 and HB3 a G-A transition at position 965, resulting in both cases in a non-conservative amino acid substitution. The data presented, together with the results of the immunological studies pub lished previously [10][11][12], show clearly that, simi larly to the sexual stage specific surface antigens Pfs25 [16] and Pfs230 [17], the antigenic diversity of Pfs48/45 as it occurs in the field is exceedingly low. This observation further strengthens earlier conclu sions that Pfs48/45 is an important candidate anti gen for the development of a transmission-blocking subunit vaccine.…”

“…Because epitopes other than Ha and lie are highly conserved [10][11][12], initially of the other strains only the DNA region of Pfs48/45 that is different in NF54 and 7G8 (see above) was sequenced (Fig. 1A).…”

“…Therefore we analyzed the nucleotide sequences of the Pfs48/45 genes in 7 in vitro culti vated P. falciparum strains collected from various [4], Liberia (LE5, LF4) [5], Ghana (GH1), Honduras (HB3) [6], Malaysia (CAMP) [7], and Indochina (Dd2) [8], and compared these with that of NF54 [l], thought to be of African origin [9], Immunological studies with Pfs48/45 specific monoclonal antibodies have shown that antigen Pfs48/45 contains at least 5 B-cell epitopes: I, Ila or lie, lib, III and IV [10][11][12], of which the first 4 are tertiary structure dependent. The only polymorphic epitopes identified thus far are Ila and lie, which behave as though they are mutually exclusive [12], Because epitope Ila is absent from gene Pfs48/45 of strain NF54, but present in that of 7G8 [11,12], and conversely epitope lie is absent from 7G8 but pre sent in NF54 [12] (Pieter Beckers and Ton Lensen, personal communication), the entire nucleotide se quence 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 pre viously described [1], Subsequently the PCR prod ucts were sequenced without intermediate subcloning [13].…”