Construction of a synthetic immunogen: use of the natural immunomodulator polytuftsin in malaria vaccines against RESA antigen of Plasmodium falciparum.
Polytuftsin, a 35-40-unit repeat of the naturally occurring tetrapeptide tuftsin (TKPR), was chemically linked to EENVEHDA and DDEHVEEPTVA repeat sequences of ring-infected erythrocyte surface antigen protein (an asexual blood-stage antigen) of Plasmodium falciparum. These synthetic constructs were tested for their humoral and cellular immune responses in five inbred strains of mice with different genetic backgrounds (H-2a, H-2b, H-2d, H-2k and H-2i). Mice immunized with these constructs showed higher antibody titres, secondary immune responses and antigen-induced T-cell proliferation compared with the peptide dimers alone. Sera from mice immunized with both the constructs inhibited merozoite invasion of erythrocytes in vitro by 60-80% at 1:10 antisera dilution. Polytuftsin alone proved to be a very poor immunogen in our studies, since no anti-tuftsin antibodies could be detected in the sera. Therefore, we conclude that the synthetic constructs described here could be useful for the development of subunit malaria vaccines.
Pawan
K
K
Department of Biochemistry, All India Institute of Medical Sciences, New Delhi.
Ivanov
B B
BB
Kabilan
L
L
Rao
D N
DN
D000595:Amino Acid Sequence; D000818:Animals; D000913:Antibodies, Protozoan / Q000096:biosynthesis; D000953:Antigens, Protozoan / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D000954:Antigens, Surface / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D002478:Cells, Cultured; D004306:Dose-Response Relationship, Immunologic; D004337:Drug Carriers; D004591:Electrophoresis, Polyacrylamide Gel; D000939:Epitopes / Q000276:immunology; D008213:Lymphocyte Activation; D017780:Malaria Vaccines / Q000276:immunology*; D020066:Merozoite Surface Protein 1; D051379:Mice; D008807:Mice, Inbred BALB C; D008815:Mice, Inbred Strains / Q000235:genetics; D008969:Molecular Sequence Data; D010586:Phagocytes / Q000276:immunology; D010963:Plasmodium falciparum / Q000235:genetics / Q000276:immunology*; D011108:Polymers / Q000737:chemistry / Q000494:pharmacology*; D011498:Protein Precursors / Q000097:blood; D015800:Protozoan Proteins / Q000097:blood / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D014405:Tuftsin / Q000737:chemistry / Q000494:pharmacology*; D014611:Vaccination; D018074:Vaccines, Conjugate / Q000276:immunology*
D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D000954:Antigens, Surface; D004337:Drug Carriers; D000939:Epitopes; D017780:Malaria Vaccines; D020066:Merozoite Surface Protein 1; D011108:Polymers; D011498:Protein Precursors; D015800:Protozoan Proteins; D018074:Vaccines, Conjugate; C050256:ring-infected erythrocyte surface antigen (RESA), Plasmodium falciparum; C053968:polytuftsin; D014405:Tuftsin