Immunogenicity of recombinant Plasmodium falciparum SERA proteins in rodents.
We have expressed defined regions of the serine-repeat antigen (SERA) of the Honduras-1 strain of Plasmodium falciparum in the yeast Saccharomyces cerevisiae. Amino-terminal domains of the natural SERA protein have been shown previously to be targets for parasite-inhibitory murine monoclonal antibodies. Two recombinant SERA antigens were selected for purification and immunological analysis. The first (SERA 1), corresponding to amino acids 24-285 of the natural SERA precursor, was expressed by the ubiquitin fusion method. This allowed for in vivo cleavage by endogenous yeast ubiquitin hydrolase, and subsequent isolation of the mature polypeptide. The second, larger protein (SERA N), encompassing amino acids 24-506, was expressed at only low levels using this system, but could be isolated in high yields when fused to human gamma-interferon (gamma-IFN). Each purified protein was used to immunize mice with either Freund's adjuvant or a muramyl tripeptide adjuvant that has been used in humans. Sera from immunized mice were shown to be capable of in vitro inhibition of invasion of erythrocytes by the Honduras-1 strain of P. falciparum. The results suggest that a recombinant SERA antigen may be an effective component of a candidate malaria vaccine.
Barr
P J
PJ
Chiron Corporation, Emeryville, CA 94608.
Inselburg
J
J
Green
K M
KM
Kansopon
J
J
Hahm
B K
BK
Gibson
H L
HL
Lee-Ng
C T
CT
Bzik
D J
DJ
Li
W B
WB
Bathurst
I C
IC
D000818:Animals; D000913:Antibodies, Protozoan / Q000096:biosynthesis; D000953:Antigens, Protozoan / Q000235:genetics / Q000276:immunology*; D000954:Antigens, Surface / Q000235:genetics / Q000276:immunology*; D001483:Base Sequence; D002478:Cells, Cultured; D003001:Cloning, Molecular; D004912:Erythrocytes / Q000469:parasitology; D015870:Gene Expression; D051379:Mice; D008969:Molecular Sequence Data; D010957:Plasmids; D010963:Plasmodium falciparum / Q000235:genetics / Q000276:immunology*; D015800:Protozoan Proteins / Q000235:genetics / Q000276:immunology*; D016052:Protozoan Vaccines; D012441:Saccharomyces cerevisiae / Q000235:genetics; D012995:Solubility
D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D000954:Antigens, Surface; D015800:Protozoan Proteins; D016052:Protozoan Vaccines; C057495:serine repeat antigen, Plasmodium