Use of adjuvant containing mycobacterial cell-wall skeleton, monophosphoryl lipid A, and squalane in malaria circumsporozoite protein vaccine.
Human immune responses to modern synthetic and recombinant peptide vaccines administered with the standard adjuvant, aluminum hydroxide, tend to be poor, hence the search for better adjuvants. Antibody responses to a Plasmodium falciparum circumsporozoite (CS) protein vaccine, R32NS1(81), administered with an adjuvant containing cell-wall skeleton of mycobacteria and monophosphoryl lipid A in squalane (MPL/CWS) have been compared to responses to the same immunogen administered with aluminum hydroxide. 2 weeks after the third dose the following indices were greater in the 5 patients who received MPL/CWS than in controls (p less than 0.05): the geometric mean concentration (2.0 vs 25.4 microgram/ml) and avidity index of antibodies to the P falciparum CS protein by ELISA, the geometric mean titre to P falciparum sporozoites by IFAT (1/115 vs 1/1600), and the geometric mean inhibition of sporozoite invasion of hepatoma cells in vitro (37.6 vs 90.3%). For R32NS1(81) MPL/CWS is superior to aluminum hydroxide as an adjuvant, and the data support the evaluation of this complex as an adjuvant for other vaccines.
Rickman
L S
LS
Division of Infectious Diseases, National Naval Medical Center, Bethesda, Maryland 20852.
Gordon
D M
DM
Wistar
R
R
Krzych
U
U
Gross
M
M
Hollingdale
M R
MR
Egan
J E
JE
Chulay
J D
JD
Hoffman
S L
SL
D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000328:Adult; D000818:Animals; D000913:Antibodies, Protozoan / Q000032:analysis; D000915:Antibody Affinity / Q000187:drug effects; D002473:Cell Wall / Q000382:microbiology; D006801:Humans; D007074:Immunoglobulin G / Q000032:analysis; D008050:Lipid A / Q000008:administration & dosage / Q000031:analogs & derivatives; D017780:Malaria Vaccines; D008297:Male; D009161:Mycobacterium / Q000166:cytology; D010963:Plasmodium falciparum / Q000276:immunology*; D016052:Protozoan Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology*; D011993:Recombinant Fusion Proteins; D013185:Squalene / Q000008:administration & dosage; D014614:Vaccines, Synthetic / Q000009:adverse effects / Q000276:immunology*
D000276:Adjuvants, Immunologic; D000913:Antibodies, Protozoan; D007074:Immunoglobulin G; D008050:Lipid A; D017780:Malaria Vaccines; D016052:Protozoan Vaccines; C068418:R 32NS1(81); D011993:Recombinant Fusion Proteins; D014614:Vaccines, Synthetic; D013185:Squalene; C048436:monophosphoryl lipid A