Safety and immunogenicity in volunteers of a recombinant Plasmodium falciparum circumsporozoite protein malaria vaccine produced in Lepidopteran cells.
A recombinant Plasmodium falciparum circumsporozoite (CS) antigen (rPfCSA) was produced in insect cells using a baculovirus expression vector containing the entire CS gene. This near full-length CS antigen was adsorbed onto aluminium phosphate for use as a malaria vaccine. In a study of safety and immunogenicity, 20 volunteers were divided into four groups of five each and inoculated intramuscularly with 10, 100, 500 or 1000 micrograms of vaccine. Primary vaccinations were followed by two booster immunizations at 2 and 6 months. Three volunteers developed prominent local reactions manifested as tenderness, redness and swelling at the injection site following the second or third vaccination. All symptoms resolved spontaneously within 72 h. Postimmunization sera from six of 20 volunteers showed seroconversions as measured by Western blot, using rPfCSA as antigen. However, specific anti-CS protein antibody could not be detected by indirect immunoflourescence against intact sporozoites or by ELISA using rPfCSA or peptide to the repeat region. In addition, 18 of 20 volunteers developed antibody to baculovirus proteins as determined by ELISA and/or Western blot. Antigen-driven replication studies using peripheral blood mononuclear cells from vaccinees failed to detect proliferative responses specific to CS protein. This recombinant CS protein vaccine, as formulated, was minimally immunogenic in humans.
Herrington
D A
DA
Department of Medicine, University of Maryland, Baltimore 21201.
Losonsky
G A
GA
Smith
G
G
Volvovitz
F
F
Cochran
M
M
Jackson
K
K
Hoffman
S L
SL
Gordon
D M
DM
Levine
M M
MM
Edelman
R
R
D000328:Adult; D000595:Amino Acid Sequence; D000818:Animals; D000913:Antibodies, Protozoan / Q000096:biosynthesis*; D000914:Antibodies, Viral / Q000096:biosynthesis; D000953:Antigens, Protozoan / Q000096:biosynthesis / Q000276:immunology*; D016367:Baculoviridae / Q000235:genetics / Q000276:immunology; D015153:Blotting, Western; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007117:Immunization, Secondary; D007915:Lepidoptera; D008297:Male; D008969:Molecular Sequence Data; D010963:Plasmodium falciparum / Q000276:immunology*; D015800:Protozoan Proteins; D016052:Protozoan Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology*; D014611:Vaccination; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology
D000913:Antibodies, Protozoan; D000914:Antibodies, Viral; D000953:Antigens, Protozoan; D015800:Protozoan Proteins; D016052:Protozoan Vaccines; D014614:Vaccines, Synthetic; C041595:circumsporozoite protein, Protozoan