Identification of Plasmodium falciparum antigens by antigenic analysis of genomic and proteomic data.
The recent explosion in genomic sequencing has made available a wealth of data that can now be analyzed to identify protein antigens, potential targets for vaccine development. Here we present, in the context of Plasmodium falciparum, a strategy that rapidly identifies target antigens from large and complex genomes. Sixteen antigenic proteins recognized by volunteers immunized with radiation-attenuated P. falciparum sporozoites, but not by mock immunized controls, were identified. Several of these were more antigenic than previously identified and well characterized P. falciparum-derived protein antigens. The data suggest that immune responses to Plasmodium are dispersed on a relatively large number of parasite antigens. These studies have implications for our understanding of immunodominance and breadth of responses to complex pathogens.
Doolan
Denise L
DL
Malaria Program, Naval Medical Research Center, Silver Spring, MD 20910-7500, USA.
Southwood
Scott
S
Freilich
Daniel A
DA
Sidney
John
J
Graber
Norma L
NL
Shatney
Lori
L
Bebris
Lolita
L
Florens
Laurence
L
Dobano
Carlota
C
Witney
Adam A
AA
Appella
Ettore
E
Hoffman
Stephen L
SL
Yates
John R
JR
Carucci
Daniel J
DJ
Sette
Alessandro
A
D000328:Adult; D000465:Algorithms; D000483:Alleles; D000818:Animals; D000953:Antigens, Protozoan / Q000235:genetics* / Q000302:isolation & purification; D017125:Genes, Protozoan; D018503:Genome, Protozoan; D023281:Genomics; D006801:Humans; D007114:Immunization; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000096:biosynthesis; D017780:Malaria Vaccines / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D010963:Plasmodium falciparum / Q000235:genetics* / Q000276:immunology*; D040901:Proteomics; D015800:Protozoan Proteins / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification; D013601:T-Lymphocytes / Q000276:immunology
D000953:Antigens, Protozoan; D017780:Malaria Vaccines; D015800:Protozoan Proteins; D007371:Interferon-gamma