Induction of crossreactive antibodies against the Plasmodium falciparum variant protein.
The variant antigen Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1), present on the surface of P. falciparum-parasitized erythrocytes (PE), plays a central role in naturally acquired immunity, although antibodies to PfEMP1 are predominantly variant specific. To overcome this major limitation for vaccine development, we immunized mice with three cysteine-rich interdomain 1 (CIDR1) domains of PfEMP1 that have the critical function of binding the PE to CD36 on endothelium and thus preventing spleen-dependent killing of the parasite. The immunizations consisted of different combinations of three CIDR1 encoded by DNA followed by recombinant protein boost. Immunizations with a single variant in a prime-boost regimen induced no or low cross-reactivity toward heterologous CIDR1; however, a broad range of crossreactivity was detected in mice that were immunized with all three variants simultaneously. The induced crossreactivity suggests that an anti-PfEMP1 vaccine may be possible.
Gratepanche
Sylvie
S
Malaria Vaccine Development Unit, National Institute of Allergy and Infectious Diseases/National Institutes of Health, Rockville, MD 20852, USA.
Gamain
Benoit
B
Smith
Joseph D
JD
Robinson
Bridget A
BA
Saul
Allan
A
Miller
Louis H
LH
D000818:Animals; D000913:Antibodies, Protozoan / Q000276:immunology*; D001483:Base Sequence; D016466:CHO Cells; D003001:Cloning, Molecular; D006224:Cricetinae; D003429:Cross Reactions / Q000276:immunology*; D017931:DNA Primers; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D016778:Malaria, Falciparum / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D010963:Plasmodium falciparum / Q000276:immunology*; D015800:Protozoan Proteins / Q000235:genetics* / Q000276:immunology* / Q000302:isolation & purification; D016052:Protozoan Vaccines; D011994:Recombinant Proteins / Q000276:immunology; D015183:Restriction Mapping; D014162:Transfection
D000913:Antibodies, Protozoan; D017931:DNA Primers; D015800:Protozoan Proteins; D016052:Protozoan Vaccines; D011994:Recombinant Proteins; C085731:erythrocyte membrane protein 1, Plasmodium falciparum