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
| Autor: | S. Kotani, C. Hashiro, Wasim A. Siddiqui, S. E. Case, Sandra P. Chang, T. Shiba, Leslie Q. Tam, S. Kusumoto, George Hui |
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| Rok vydání: | 1991 |
| Předmět: |
medicine.medical_treatment
Freund's Adjuvant Plasmodium falciparum Immunology Antibody Affinity Antibodies Protozoan Monophosphoryl Lipid A Antigens Protozoan Enzyme-Linked Immunosorbent Assay Biology Pharmacology Microbiology chemistry.chemical_compound parasitic diseases medicine Animals Merozoite surface protein Malaria vaccine Immune Sera Antibody titer biology.organism_classification Lipid A Infectious Diseases chemistry Freund's adjuvant Antigens Surface Immunization Parasitology Rabbits Acetylmuramyl-Alanyl-Isoglutamine Adjuvant Muramyl dipeptide Research Article |
| Zdroj: | Infection and Immunity. 59:1585-1591 |
| ISSN: | 1098-5522 0019-9567 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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