Safety, immunogenicity, and efficacy of Plasmodium falciparum repeatless circumsporozoite protein vaccine encapsulated in liposomes.
Seventeen malaria-naive volunteers received a recombinant Plasmodium falciparum vaccine (RLF) containing the carboxy- and the amino-terminal of the circumsporozoite protein (CSP) antigen without the central tetrapeptide repeats. The vaccine was formulated in liposomes with either a low or high dose of 3-deacylated monophosphoryl lipid A (MPL) and administered with alum by intramuscular injection. Both formulations were well tolerated and immunogenic. MPL increased sporozoite antibody titers measured by ELISA, Western blot, and immunofluorescence assay. One high-dose MPL vaccine formulation recipient developed a CSP-specific cytotoxic T lymphocyte response. After homologous sporozoite challenge, immunized volunteers developed patent malaria. There was no correlation between prepatent period and antibody titers to the amino- or carboxy-terminal. The absence of delay in patency argues against inclusion of the amino-terminal in future vaccines. A significant cytotoxic T lymphocyte response may have been suppressed by the inclusion of alum as an adjuvant.
Heppner
D G
DG
Department of Membrane Biochemistry, Walter Reed Army Institute of Research, Washington, DC, USA.
Gordon
D M
DM
Gross
M
M
Wellde
B
B
Leitner
W
W
Krzych
U
U
Schneider
I
I
Wirtz
R A
RA
Richards
R L
RL
Trofa
A
A
Hall
T
T
Sadoff
J C
JC
Boerger
P
P
Alving
C R
CR
Sylvester
D R
DR
Porter
T G
TG
Ballou
W R
WR
D000293:Adolescent; D000328:Adult; D000953:Antigens, Protozoan / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use; D003602:Cytotoxicity, Immunologic; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers; D005260:Female; D006801:Humans; D008081:Liposomes; D008213:Lymphocyte Activation; D017780:Malaria Vaccines / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*; D016778:Malaria, Falciparum / Q000517:prevention & control*; D008297:Male; D008875:Middle Aged; D015800:Protozoan Proteins / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*; D012091:Repetitive Sequences, Nucleic Acid; D012449:Safety; D014614:Vaccines, Synthetic / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*
D000953:Antigens, Protozoan; D004337:Drug Carriers; D008081:Liposomes; D017780:Malaria Vaccines; D015800:Protozoan Proteins; D014614:Vaccines, Synthetic; C041595:circumsporozoite protein, Protozoan