Document Detail


Multiple antigen peptide vaccines against Plasmodium falciparum malaria.
MedLine Citation:
PMID:  20823210     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The multiple antigen peptide (MAP) approach is an effective method to chemically synthesize and deliver multiple T-cell and B-cell epitopes as the constituents of a single immunogen. Here we report on the design, chemical synthesis, and immunogenicity of three Plasmodium falciparum MAP vaccines that incorporated antigenic epitopes from the sporozoite, liver, and blood stages of the life cycle. Antibody and cellular responses were determined in three inbred (C57BL/6, BALB/c, and A/J) strains, one congenic (HLA-A2 on the C57BL/6 background) strain, and one outbred strain (CD1) of mice. All three MAPs were immunogenic and induced both antibody and cellular responses, albeit in a somewhat genetically restricted manner. Antibodies against MAP-1, MAP-2, and MAP-3 had an antiparasite effect that was also dependent on the mouse major histocompatibility complex background. Anti-MAP-1 (CSP-based) antibodies blocked the invasion of HepG2 liver cells by P. falciparum sporozoites (highest, 95.16% in HLA-A2 C57BL/6; lowest, 11.21% in BALB/c). Furthermore, antibodies generated following immunizations with the MAP-2 (PfCSP, PfLSA-1, PfMSP-1(42), and PfMSP-3b) and MAP-3 (PfRAP-1, PfRAP-2, PfSERA, and PfMSP-1(42)) vaccines were able to reduce the growth of blood stage parasites in erythrocyte cultures to various degrees. Thus, MAP-based vaccines remain a viable option to induce effective antibody and cellular responses. These results warrant further development and preclinical and clinical testing of the next generation of candidate MAP vaccines that are based on the conserved protective epitopes from Plasmodium antigens that are widely recognized by populations of divergent HLA types from around the world.
Authors:
Babita Mahajan; Jay A Berzofsky; Robert A Boykins; Victoria Majam; Hong Zheng; Rana Chattopadhyay; Patricia de la Vega; J Kathleen Moch; J David Haynes; Igor M Belyakov; Hira L Nakhasi; Sanjai Kumar
Publication Detail:
Type:  Journal Article     Date:  2010-09-07
Journal Detail:
Title:  Infection and immunity     Volume:  78     ISSN:  1098-5522     ISO Abbreviation:  Infect. Immun.     Publication Date:  2010 Nov 
Date Detail:
Created Date:  2010-10-19     Completed Date:  2010-11-12     Revised Date:  2013-05-28    
Medline Journal Info:
Nlm Unique ID:  0246127     Medline TA:  Infect Immun     Country:  United States    
Other Details:
Languages:  eng     Pagination:  4613-24     Citation Subset:  IM    
Affiliation:
Division of Emerging and Transfusion Transmitted Diseases, Center for Biologics Evaluation and Research, Food and Drug Administration, Rockville, MD 20852, USA.
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MeSH Terms
Descriptor/Qualifier:
Amino Acid Sequence
Animals
Animals, Outbred Strains
Antibodies, Protozoan / blood
Antigens, Protozoan* / chemistry,  immunology
Cell Line
Cell Line, Tumor
Cells, Cultured
Drug Design
Epitopes, B-Lymphocyte / chemistry,  immunology
Epitopes, T-Lymphocyte / chemistry,  immunology
Erythrocytes / parasitology
Female
HLA-A2 Antigen / genetics,  metabolism
Hepatocytes / parasitology
Humans
Immunization
Malaria Vaccines* / administration & dosage,  chemical synthesis,  chemistry,  immunology
Malaria, Falciparum / immunology,  prevention & control*
Mice
Mice, Congenic
Mice, Inbred Strains
Molecular Sequence Data
Plasmodium falciparum / immunology,  pathogenicity
T-Lymphocytes / immunology
Vaccines, Subunit* / administration & dosage,  chemical synthesis,  chemistry,  immunology
Vaccines, Synthetic* / administration & dosage,  chemistry,  immunology
Chemical
Reg. No./Substance:
0/Antibodies, Protozoan; 0/Antigens, Protozoan; 0/Epitopes, B-Lymphocyte; 0/Epitopes, T-Lymphocyte; 0/HLA-A2 Antigen; 0/Malaria Vaccines; 0/Vaccines, Subunit; 0/Vaccines, Synthetic
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