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
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
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DOI：
10.1128/iai.59.5.1585-1591.1991
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发表时间：
1991-05-01
影响因子：
3.1
通讯作者：
KOTANI, S
中科院分区：
文献类型：
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作者：
HUI, GSN;TAM, LQ;KOTANI, S
恶性疟原虫主要裂殖子表面蛋白（gp 195）是针对致死性疟疾的保护性抗原。然而，越来越多的证据表明，疟疾疫苗的效力将需要一种对人类使用安全的强佐剂。我们比较了两种低毒性合成免疫调节剂B30-MDP（亲脂性胞壁酰二肽衍生物）和LA-15-PH（单磷酰脂质A的合成等效物）与弗氏完全佐剂（FCA）在引发对gp 195的抗体应答方面的功效。用天然gp 195和B30-MDP、LA-15-PH或两者的组合免疫家兔，脂质体作为媒介物。氢氧化铝和FCA用作参比佐剂。结果显示，与FCA相比，基于B30-MDP单独或与LA-15-PH组合的佐剂制剂诱导针对gp 195的高抗体滴度。LA-15-PH单独使用效果较差。氢氧化铝诱导显著较低的抗体滴度。在体外寄生虫生长抑制试验中评价了由不同佐剂诱导的兔抗gp 195抗体的功能活性，该试验先前显示与Aotus猴模型中的抗gp 195免疫相关。用B30-MDP-LA-15-PH免疫的所有兔和用B30-MDP单独免疫的三只兔中的两只产生强烈抑制寄生虫生长的血清。生长抑制程度与FCA相似。接受B30-MDP-LA-15-PH的家兔的抗体滴度与体外生长抑制程度密切相关。我们的研究结果提供了强有力的证据，表明基于合成B30-MDP和LA-15-PH的佐剂制剂可以取代FCA作为佐剂，刺激针对gp 195的保护性免疫。
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.