Synthetic low-toxicity muramyl dipeptide and monophosphoryl lipid A replace Freund complete adjuvant in inducing growth-inhibitory antibodies to the Plasmodium falciparum major merozoite surface protein, gp195.
The Plasmodium falciparum major merozoite surface protein (gp195) is a protective antigen against lethal malaria. However, increasing evidence indicates that the efficacy of a malaria vaccine will require a strong adjuvant that is safe for human use. We compared the efficacies of two low-toxicity synthetic immunomodulators, B30-MDP (a lipophilic muramyl dipeptide derivative) and LA-15-PH (a synthetic equivalent of monophosphoryl lipid A), with that of Freund complete adjuvant (FCA) in eliciting an antibody response to gp195. Rabbits were immunized with native gp195 and B30-MDP, LA-15-PH, or the two in combination, with liposomes as the vehicle. Aluminum hydroxide and FCA were used as reference adjuvants. Results showed that adjuvant formulations based on B30-MDP alone or in combination with LA-15-PH induced high antibody titers to gp195, as compared with FCA. LA-15-PH alone was less effective. Aluminum hydroxide induced significantly lower antibody titers. The functional activity of the rabbit anti-gp195 antibodies induced by different adjuvants was evaluated in an in vitro parasite growth inhibition assay previously shown to correlate with anti-gp195 immunity in the Aotus monkey model. All rabbits immunized with B30-MDP-LA-15-PH and two of three rabbits immunized with B30-MDP alone produced sera that strongly inhibited parasite growth. The degree of growth inhibition was similar to that with FCA. The antibody titers of the rabbits receiving B30-MDP-LA-15-PH strongly correlated with the degree of in vitro growth inhibition. Our findings provided strong evidence that adjuvant formulations based on synthetic B30-MDP and LA-15-PH can replace FCA as adjuvants in stimulating protective immunity specific for gp195.
Hui
G S
GS
Department of Tropical Medicine, School of Medicine, University of Hawaii, Honolulu 96816.
Tam
L Q
LQ
Chang
S P
SP
Case
S E
SE
Hashiro
C
C
Siddiqui
W A
WA
Shiba
T
T
Kusumoto
S
S
Kotani
S
S
D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000276:immunology*; D000818:Animals; D000913:Antibodies, Protozoan / Q000096:biosynthesis*; D000915:Antibody Affinity; D000953:Antigens, Protozoan / Q000276:immunology*; D000954:Antigens, Surface / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005620:Freund's Adjuvant; D007106:Immune Sera / Q000276:immunology; D007114:Immunization; D008050:Lipid A / Q000276:immunology*; D010963:Plasmodium falciparum / Q000254:growth & development / Q000276:immunology*; D011817:Rabbits
D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D000954:Antigens, Surface; D007106:Immune Sera; D008050:Lipid A; C057273:antigen gp195, Plasmodium; D000119:Acetylmuramyl-Alanyl-Isoglutamine; D005620:Freund's Adjuvant