Vaccine potentials of an intrinsically unstructured fragment derived from the blood stage-associated Plasmodium falciparum protein PFF0165c.
We have identified new malaria vaccine candidates through the combination of bioinformatics prediction of stable protein domains in the Plasmodium falciparum genome, chemical synthesis of polypeptides, in vitro biological functional assays, and association of an antigen-specific antibody response with protection against clinical malaria. Within the predicted open reading frame of P. falciparum hypothetical protein PFF0165c, several segments with low hydrophobic amino acid content, which are likely to be intrinsically unstructured, were identified. The synthetic peptide corresponding to one such segment (P27A) was well recognized by sera and peripheral blood mononuclear cells of adults living in different regions where malaria is endemic. High antibody titers were induced in different strains of mice and in rabbits immunized with the polypeptide formulated with different adjuvants. These antibodies recognized native epitopes in P. falciparum-infected erythrocytes, formed distinct bands in Western blots, and were inhibitory in an in vitro antibody-dependent cellular inhibition parasite-growth assay. The immunological properties of P27A, together with its low polymorphism and association with clinical protection from malaria in humans, warrant its further development as a malaria vaccine candidate.
Olugbile
S
S
Centre Hospitalier Universitaire Vaudois CHUV, Lausanne, Switzerland.
Kulangara
C
C
Bang
G
G
Bertholet
S
S
Suzarte
E
E
Villard
V
V
Frank
G
G
Audran
R
R
Razaname
A
A
Nebie
I
I
Awobusuyi
O
O
Spertini
F
F
Kajava
A V
AV
Felger
I
I
Druilhe
P
P
Corradin
G
G
D000328:Adult; D000595:Amino Acid Sequence; D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood; D000953:Antigens, Protozoan / Q000235:genetics / Q000276:immunology*; D006801:Humans; D017780:Malaria Vaccines / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008969:Molecular Sequence Data; D010963:Plasmodium falciparum / Q000235:genetics / Q000276:immunology*; D011110:Polymorphism, Genetic; D015800:Protozoan Proteins / Q000235:genetics / Q000276:immunology*; D011817:Rabbits; D014614:Vaccines, Synthetic / Q000235:genetics / Q000276:immunology; D055815:Young Adult
D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D017780:Malaria Vaccines; D015800:Protozoan Proteins; C579321:Tex1 protein, Plasmodium falciparum; D014614:Vaccines, Synthetic