Strains used in whole organism Plasmodium falciparum vaccine trials differ in genome structure, sequence, and immunogenic potential
Background Plasmodium falciparum (Pf) whole-organism sporozoite vaccines have been shown to provide significant protection against controlled human malaria infection (CHMI) in clinical trials. Initial CHMI studies showed significantly higher durable protection against homologous than heterologous st...
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| Vydáno v: | Genome medicine Ročník 12; číslo 1; s. 6 - 17 |
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| Hlavní autoři: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
| Médium: | Journal Article |
| Jazyk: | angličtina |
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London
BioMed Central
08.01.2020
BioMed Central Ltd Springer Nature B.V BMC |
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| ISSN: | 1756-994X, 1756-994X |
| On-line přístup: | Získat plný text |
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| Abstract | Background
Plasmodium falciparum
(Pf) whole-organism sporozoite vaccines have been shown to provide significant protection against controlled human malaria infection (CHMI) in clinical trials. Initial CHMI studies showed significantly higher durable protection against homologous than heterologous strains, suggesting the presence of strain-specific vaccine-induced protection. However, interpretation of these results and understanding of their relevance to vaccine efficacy have been hampered by the lack of knowledge on genetic differences between vaccine and CHMI strains, and how these strains are related to parasites in malaria endemic regions.
Methods
Whole genome sequencing using long-read (Pacific Biosciences) and short-read (Illumina) sequencing platforms was conducted to generate de novo genome assemblies for the vaccine strain, NF54, and for strains used in heterologous CHMI (7G8 from Brazil, NF166.C8 from Guinea, and NF135.C10 from Cambodia). The assemblies were used to characterize sequences in each strain relative to the reference 3D7 (a clone of NF54) genome. Strains were compared to each other and to a collection of clinical isolates (sequenced as part of this study or from public repositories) from South America, sub-Saharan Africa, and Southeast Asia.
Results
While few variants were detected between 3D7 and NF54, we identified tens of thousands of variants between NF54 and the three heterologous strains. These variants include SNPs, indels, and small structural variants that fall in regulatory and immunologically important regions, including transcription factors (such as PfAP2-L and PfAP2-G) and pre-erythrocytic antigens that may be key for sporozoite vaccine-induced protection. Additionally, these variants directly contributed to diversity in immunologically important regions of the genomes as detected through in silico CD8
+
T cell epitope predictions. Of all heterologous strains, NF135.C10 had the highest number of unique predicted epitope sequences when compared to NF54. Comparison to global clinical isolates revealed that these four strains are representative of their geographic origin despite long-term culture adaptation; of note, NF135.C10 is from an admixed population, and not part of recently formed subpopulations resistant to artemisinin-based therapies present in the Greater Mekong Sub-region.
Conclusions
These results will assist in the interpretation of vaccine efficacy of whole-organism vaccines against homologous and heterologous CHMI. |
|---|---|
| AbstractList | Background Plasmodium falciparum (Pf) whole-organism sporozoite vaccines have been shown to provide significant protection against controlled human malaria infection (CHMI) in clinical trials. Initial CHMI studies showed significantly higher durable protection against homologous than heterologous strains, suggesting the presence of strain-specific vaccine-induced protection. However, interpretation of these results and understanding of their relevance to vaccine efficacy have been hampered by the lack of knowledge on genetic differences between vaccine and CHMI strains, and how these strains are related to parasites in malaria endemic regions. Methods Whole genome sequencing using long-read (Pacific Biosciences) and short-read (Illumina) sequencing platforms was conducted to generate de novo genome assemblies for the vaccine strain, NF54, and for strains used in heterologous CHMI (7G8 from Brazil, NF166.C8 from Guinea, and NF135.C10 from Cambodia). The assemblies were used to characterize sequences in each strain relative to the reference 3D7 (a clone of NF54) genome. Strains were compared to each other and to a collection of clinical isolates (sequenced as part of this study or from public repositories) from South America, sub-Saharan Africa, and Southeast Asia. Results While few variants were detected between 3D7 and NF54, we identified tens of thousands of variants between NF54 and the three heterologous strains. These variants include SNPs, indels, and small structural variants that fall in regulatory and immunologically important regions, including transcription factors (such as PfAP2-L and PfAP2-G) and pre-erythrocytic antigens that may be key for sporozoite vaccine-induced protection. Additionally, these variants directly contributed to diversity in immunologically important regions of the genomes as detected through in silico CD8+ T cell epitope predictions. Of all heterologous strains, NF135.C10 had the highest number of unique predicted epitope sequences when compared to NF54. Comparison to global clinical isolates revealed that these four strains are representative of their geographic origin despite long-term culture adaptation; of note, NF135.C10 is from an admixed population, and not part of recently formed subpopulations resistant to artemisinin-based therapies present in the Greater Mekong Sub-region. Conclusions These results will assist in the interpretation of vaccine efficacy of whole-organism vaccines against homologous and heterologous CHMI. Abstract Background Plasmodium falciparum (Pf) whole-organism sporozoite vaccines have been shown to provide significant protection against controlled human malaria infection (CHMI) in clinical trials. Initial CHMI studies showed significantly higher durable protection against homologous than heterologous strains, suggesting the presence of strain-specific vaccine-induced protection. However, interpretation of these results and understanding of their relevance to vaccine efficacy have been hampered by the lack of knowledge on genetic differences between vaccine and CHMI strains, and how these strains are related to parasites in malaria endemic regions. Methods Whole genome sequencing using long-read (Pacific Biosciences) and short-read (Illumina) sequencing platforms was conducted to generate de novo genome assemblies for the vaccine strain, NF54, and for strains used in heterologous CHMI (7G8 from Brazil, NF166.C8 from Guinea, and NF135.C10 from Cambodia). The assemblies were used to characterize sequences in each strain relative to the reference 3D7 (a clone of NF54) genome. Strains were compared to each other and to a collection of clinical isolates (sequenced as part of this study or from public repositories) from South America, sub-Saharan Africa, and Southeast Asia. Results While few variants were detected between 3D7 and NF54, we identified tens of thousands of variants between NF54 and the three heterologous strains. These variants include SNPs, indels, and small structural variants that fall in regulatory and immunologically important regions, including transcription factors (such as PfAP2-L and PfAP2-G) and pre-erythrocytic antigens that may be key for sporozoite vaccine-induced protection. Additionally, these variants directly contributed to diversity in immunologically important regions of the genomes as detected through in silico CD8+ T cell epitope predictions. Of all heterologous strains, NF135.C10 had the highest number of unique predicted epitope sequences when compared to NF54. Comparison to global clinical isolates revealed that these four strains are representative of their geographic origin despite long-term culture adaptation; of note, NF135.C10 is from an admixed population, and not part of recently formed subpopulations resistant to artemisinin-based therapies present in the Greater Mekong Sub-region. Conclusions These results will assist in the interpretation of vaccine efficacy of whole-organism vaccines against homologous and heterologous CHMI. Plasmodium falciparum (Pf) whole-organism sporozoite vaccines have been shown to provide significant protection against controlled human malaria infection (CHMI) in clinical trials. Initial CHMI studies showed significantly higher durable protection against homologous than heterologous strains, suggesting the presence of strain-specific vaccine-induced protection. However, interpretation of these results and understanding of their relevance to vaccine efficacy have been hampered by the lack of knowledge on genetic differences between vaccine and CHMI strains, and how these strains are related to parasites in malaria endemic regions. Whole genome sequencing using long-read (Pacific Biosciences) and short-read (Illumina) sequencing platforms was conducted to generate de novo genome assemblies for the vaccine strain, NF54, and for strains used in heterologous CHMI (7G8 from Brazil, NF166.C8 from Guinea, and NF135.C10 from Cambodia). The assemblies were used to characterize sequences in each strain relative to the reference 3D7 (a clone of NF54) genome. Strains were compared to each other and to a collection of clinical isolates (sequenced as part of this study or from public repositories) from South America, sub-Saharan Africa, and Southeast Asia. While few variants were detected between 3D7 and NF54, we identified tens of thousands of variants between NF54 and the three heterologous strains. These variants include SNPs, indels, and small structural variants that fall in regulatory and immunologically important regions, including transcription factors (such as PfAP2-L and PfAP2-G) and pre-erythrocytic antigens that may be key for sporozoite vaccine-induced protection. Additionally, these variants directly contributed to diversity in immunologically important regions of the genomes as detected through in silico CD8 T cell epitope predictions. Of all heterologous strains, NF135.C10 had the highest number of unique predicted epitope sequences when compared to NF54. Comparison to global clinical isolates revealed that these four strains are representative of their geographic origin despite long-term culture adaptation; of note, NF135.C10 is from an admixed population, and not part of recently formed subpopulations resistant to artemisinin-based therapies present in the Greater Mekong Sub-region. These results will assist in the interpretation of vaccine efficacy of whole-organism vaccines against homologous and heterologous CHMI. Plasmodium falciparum (Pf) whole-organism sporozoite vaccines have been shown to provide significant protection against controlled human malaria infection (CHMI) in clinical trials. Initial CHMI studies showed significantly higher durable protection against homologous than heterologous strains, suggesting the presence of strain-specific vaccine-induced protection. However, interpretation of these results and understanding of their relevance to vaccine efficacy have been hampered by the lack of knowledge on genetic differences between vaccine and CHMI strains, and how these strains are related to parasites in malaria endemic regions. Whole genome sequencing using long-read (Pacific Biosciences) and short-read (Illumina) sequencing platforms was conducted to generate de novo genome assemblies for the vaccine strain, NF54, and for strains used in heterologous CHMI (7G8 from Brazil, NF166.C8 from Guinea, and NF135.C10 from Cambodia). The assemblies were used to characterize sequences in each strain relative to the reference 3D7 (a clone of NF54) genome. Strains were compared to each other and to a collection of clinical isolates (sequenced as part of this study or from public repositories) from South America, sub-Saharan Africa, and Southeast Asia. While few variants were detected between 3D7 and NF54, we identified tens of thousands of variants between NF54 and the three heterologous strains. These variants include SNPs, indels, and small structural variants that fall in regulatory and immunologically important regions, including transcription factors (such as PfAP2-L and PfAP2-G) and pre-erythrocytic antigens that may be key for sporozoite vaccine-induced protection. Additionally, these variants directly contributed to diversity in immunologically important regions of the genomes as detected through in silico CD8.sup.+ T cell epitope predictions. Of all heterologous strains, NF135.C10 had the highest number of unique predicted epitope sequences when compared to NF54. Comparison to global clinical isolates revealed that these four strains are representative of their geographic origin despite long-term culture adaptation; of note, NF135.C10 is from an admixed population, and not part of recently formed subpopulations resistant to artemisinin-based therapies present in the Greater Mekong Sub-region. These results will assist in the interpretation of vaccine efficacy of whole-organism vaccines against homologous and heterologous CHMI. Plasmodium falciparum (Pf) whole-organism sporozoite vaccines have been shown to provide significant protection against controlled human malaria infection (CHMI) in clinical trials. Initial CHMI studies showed significantly higher durable protection against homologous than heterologous strains, suggesting the presence of strain-specific vaccine-induced protection. However, interpretation of these results and understanding of their relevance to vaccine efficacy have been hampered by the lack of knowledge on genetic differences between vaccine and CHMI strains, and how these strains are related to parasites in malaria endemic regions.BACKGROUNDPlasmodium falciparum (Pf) whole-organism sporozoite vaccines have been shown to provide significant protection against controlled human malaria infection (CHMI) in clinical trials. Initial CHMI studies showed significantly higher durable protection against homologous than heterologous strains, suggesting the presence of strain-specific vaccine-induced protection. However, interpretation of these results and understanding of their relevance to vaccine efficacy have been hampered by the lack of knowledge on genetic differences between vaccine and CHMI strains, and how these strains are related to parasites in malaria endemic regions.Whole genome sequencing using long-read (Pacific Biosciences) and short-read (Illumina) sequencing platforms was conducted to generate de novo genome assemblies for the vaccine strain, NF54, and for strains used in heterologous CHMI (7G8 from Brazil, NF166.C8 from Guinea, and NF135.C10 from Cambodia). The assemblies were used to characterize sequences in each strain relative to the reference 3D7 (a clone of NF54) genome. Strains were compared to each other and to a collection of clinical isolates (sequenced as part of this study or from public repositories) from South America, sub-Saharan Africa, and Southeast Asia.METHODSWhole genome sequencing using long-read (Pacific Biosciences) and short-read (Illumina) sequencing platforms was conducted to generate de novo genome assemblies for the vaccine strain, NF54, and for strains used in heterologous CHMI (7G8 from Brazil, NF166.C8 from Guinea, and NF135.C10 from Cambodia). The assemblies were used to characterize sequences in each strain relative to the reference 3D7 (a clone of NF54) genome. Strains were compared to each other and to a collection of clinical isolates (sequenced as part of this study or from public repositories) from South America, sub-Saharan Africa, and Southeast Asia.While few variants were detected between 3D7 and NF54, we identified tens of thousands of variants between NF54 and the three heterologous strains. These variants include SNPs, indels, and small structural variants that fall in regulatory and immunologically important regions, including transcription factors (such as PfAP2-L and PfAP2-G) and pre-erythrocytic antigens that may be key for sporozoite vaccine-induced protection. Additionally, these variants directly contributed to diversity in immunologically important regions of the genomes as detected through in silico CD8+ T cell epitope predictions. Of all heterologous strains, NF135.C10 had the highest number of unique predicted epitope sequences when compared to NF54. Comparison to global clinical isolates revealed that these four strains are representative of their geographic origin despite long-term culture adaptation; of note, NF135.C10 is from an admixed population, and not part of recently formed subpopulations resistant to artemisinin-based therapies present in the Greater Mekong Sub-region.RESULTSWhile few variants were detected between 3D7 and NF54, we identified tens of thousands of variants between NF54 and the three heterologous strains. These variants include SNPs, indels, and small structural variants that fall in regulatory and immunologically important regions, including transcription factors (such as PfAP2-L and PfAP2-G) and pre-erythrocytic antigens that may be key for sporozoite vaccine-induced protection. Additionally, these variants directly contributed to diversity in immunologically important regions of the genomes as detected through in silico CD8+ T cell epitope predictions. Of all heterologous strains, NF135.C10 had the highest number of unique predicted epitope sequences when compared to NF54. Comparison to global clinical isolates revealed that these four strains are representative of their geographic origin despite long-term culture adaptation; of note, NF135.C10 is from an admixed population, and not part of recently formed subpopulations resistant to artemisinin-based therapies present in the Greater Mekong Sub-region.These results will assist in the interpretation of vaccine efficacy of whole-organism vaccines against homologous and heterologous CHMI.CONCLUSIONSThese results will assist in the interpretation of vaccine efficacy of whole-organism vaccines against homologous and heterologous CHMI. Background Plasmodium falciparum (Pf) whole-organism sporozoite vaccines have been shown to provide significant protection against controlled human malaria infection (CHMI) in clinical trials. Initial CHMI studies showed significantly higher durable protection against homologous than heterologous strains, suggesting the presence of strain-specific vaccine-induced protection. However, interpretation of these results and understanding of their relevance to vaccine efficacy have been hampered by the lack of knowledge on genetic differences between vaccine and CHMI strains, and how these strains are related to parasites in malaria endemic regions. Methods Whole genome sequencing using long-read (Pacific Biosciences) and short-read (Illumina) sequencing platforms was conducted to generate de novo genome assemblies for the vaccine strain, NF54, and for strains used in heterologous CHMI (7G8 from Brazil, NF166.C8 from Guinea, and NF135.C10 from Cambodia). The assemblies were used to characterize sequences in each strain relative to the reference 3D7 (a clone of NF54) genome. Strains were compared to each other and to a collection of clinical isolates (sequenced as part of this study or from public repositories) from South America, sub-Saharan Africa, and Southeast Asia. Results While few variants were detected between 3D7 and NF54, we identified tens of thousands of variants between NF54 and the three heterologous strains. These variants include SNPs, indels, and small structural variants that fall in regulatory and immunologically important regions, including transcription factors (such as PfAP2-L and PfAP2-G) and pre-erythrocytic antigens that may be key for sporozoite vaccine-induced protection. Additionally, these variants directly contributed to diversity in immunologically important regions of the genomes as detected through in silico CD8.sup.+ T cell epitope predictions. Of all heterologous strains, NF135.C10 had the highest number of unique predicted epitope sequences when compared to NF54. Comparison to global clinical isolates revealed that these four strains are representative of their geographic origin despite long-term culture adaptation; of note, NF135.C10 is from an admixed population, and not part of recently formed subpopulations resistant to artemisinin-based therapies present in the Greater Mekong Sub-region. Conclusions These results will assist in the interpretation of vaccine efficacy of whole-organism vaccines against homologous and heterologous CHMI. Keywords: P. falciparum, Malaria, Genome assembly, PfSPZ vaccine, Whole-sporozoite vaccine Background Plasmodium falciparum (Pf) whole-organism sporozoite vaccines have been shown to provide significant protection against controlled human malaria infection (CHMI) in clinical trials. Initial CHMI studies showed significantly higher durable protection against homologous than heterologous strains, suggesting the presence of strain-specific vaccine-induced protection. However, interpretation of these results and understanding of their relevance to vaccine efficacy have been hampered by the lack of knowledge on genetic differences between vaccine and CHMI strains, and how these strains are related to parasites in malaria endemic regions. Methods Whole genome sequencing using long-read (Pacific Biosciences) and short-read (Illumina) sequencing platforms was conducted to generate de novo genome assemblies for the vaccine strain, NF54, and for strains used in heterologous CHMI (7G8 from Brazil, NF166.C8 from Guinea, and NF135.C10 from Cambodia). The assemblies were used to characterize sequences in each strain relative to the reference 3D7 (a clone of NF54) genome. Strains were compared to each other and to a collection of clinical isolates (sequenced as part of this study or from public repositories) from South America, sub-Saharan Africa, and Southeast Asia. Results While few variants were detected between 3D7 and NF54, we identified tens of thousands of variants between NF54 and the three heterologous strains. These variants include SNPs, indels, and small structural variants that fall in regulatory and immunologically important regions, including transcription factors (such as PfAP2-L and PfAP2-G) and pre-erythrocytic antigens that may be key for sporozoite vaccine-induced protection. Additionally, these variants directly contributed to diversity in immunologically important regions of the genomes as detected through in silico CD8 + T cell epitope predictions. Of all heterologous strains, NF135.C10 had the highest number of unique predicted epitope sequences when compared to NF54. Comparison to global clinical isolates revealed that these four strains are representative of their geographic origin despite long-term culture adaptation; of note, NF135.C10 is from an admixed population, and not part of recently formed subpopulations resistant to artemisinin-based therapies present in the Greater Mekong Sub-region. Conclusions These results will assist in the interpretation of vaccine efficacy of whole-organism vaccines against homologous and heterologous CHMI. |
| ArticleNumber | 6 |
| Audience | Academic |
| Author | Moser, Kara A. Ouattara, Amed Ferreira, Marcelo U. Nyunt, Myaing M. Munro, James B. Travassos, Mark A. Li, Tao Dunning Hotopp, Julie C. Lon, Chanthap Silva, Joana C. Sparklin, Benjamin C. Plowe, Christopher V. Takala-Harrison, Shannon Spring, Michele D. Crabtree, Jonathan Koren, Sergey Fraser, Claire M. Lyke, Kirsten E. Stucke, Emily M. Sim, B. Kim Lee Phillippy, Adam M. Dara, Antoine Shah, Zalak Jongsakul, Krisada Laufer, Miriam K. Hoffman, Stephen L. Drábek, Elliott F. Dwivedi, Ankit Sadzewicz, Lisa Tallon, Luke J. Rodrigues, Priscila T. Saunders, David L. Sauerwein, Robert W. Adams, Matthew |
| Author_xml | – sequence: 1 givenname: Kara A. surname: Moser fullname: Moser, Kara A. organization: Institute for Genome Sciences, University of Maryland School of Medicine, Present address: Institute for Global Health and Infectious Diseases, University of North Carolina Chapel Hill – sequence: 2 givenname: Elliott F. surname: Drábek fullname: Drábek, Elliott F. organization: Institute for Genome Sciences, University of Maryland School of Medicine – sequence: 3 givenname: Ankit surname: Dwivedi fullname: Dwivedi, Ankit organization: Institute for Genome Sciences, University of Maryland School of Medicine – sequence: 4 givenname: Emily M. surname: Stucke fullname: Stucke, Emily M. organization: Center for Vaccine Development and Global Health, University of Maryland School of Medicine – sequence: 5 givenname: Jonathan surname: Crabtree fullname: Crabtree, Jonathan organization: Institute for Genome Sciences, University of Maryland School of Medicine – sequence: 6 givenname: Antoine surname: Dara fullname: Dara, Antoine organization: Center for Vaccine Development and Global Health, University of Maryland School of Medicine – sequence: 7 givenname: Zalak surname: Shah fullname: Shah, Zalak organization: Center for Vaccine Development and Global Health, University of Maryland School of Medicine – sequence: 8 givenname: Matthew surname: Adams fullname: Adams, Matthew organization: Center for Vaccine Development and Global Health, University of Maryland School of Medicine – sequence: 9 givenname: Tao surname: Li fullname: Li, Tao organization: Sanaria, Inc – sequence: 10 givenname: Priscila T. surname: Rodrigues fullname: Rodrigues, Priscila T. organization: Department of Parasitology, Institute of Biomedical Sciences, University of São Paulo – sequence: 11 givenname: Sergey surname: Koren fullname: Koren, Sergey organization: Genome Informatics Section, Computational and Statistical Genomics Branch, National Human Genome Research Institute – sequence: 12 givenname: Adam M. surname: Phillippy fullname: Phillippy, Adam M. organization: Genome Informatics Section, Computational and Statistical Genomics Branch, National Human Genome Research Institute – sequence: 13 givenname: James B. surname: Munro fullname: Munro, James B. organization: Institute for Genome Sciences, University of Maryland School of Medicine – sequence: 14 givenname: Amed surname: Ouattara fullname: Ouattara, Amed organization: Center for Vaccine Development and Global Health, University of Maryland School of Medicine – sequence: 15 givenname: Benjamin C. surname: Sparklin fullname: Sparklin, Benjamin C. organization: Institute for Genome Sciences, University of Maryland School of Medicine – sequence: 16 givenname: Julie C. surname: Dunning Hotopp fullname: Dunning Hotopp, Julie C. organization: Institute for Genome Sciences, University of Maryland School of Medicine – sequence: 17 givenname: Kirsten E. surname: Lyke fullname: Lyke, Kirsten E. organization: Center for Vaccine Development and Global Health, University of Maryland School of Medicine – sequence: 18 givenname: Lisa surname: Sadzewicz fullname: Sadzewicz, Lisa organization: Institute for Genome Sciences, University of Maryland School of Medicine – sequence: 19 givenname: Luke J. surname: Tallon fullname: Tallon, Luke J. organization: Institute for Genome Sciences, University of Maryland School of Medicine – sequence: 20 givenname: Michele D. surname: Spring fullname: Spring, Michele D. organization: Department of Bacterial and Parasitic Diseases, Armed Forces Research Institute of Medical Sciences – sequence: 21 givenname: Krisada surname: Jongsakul fullname: Jongsakul, Krisada organization: Department of Bacterial and Parasitic Diseases, Armed Forces Research Institute of Medical Sciences – sequence: 22 givenname: Chanthap surname: Lon fullname: Lon, Chanthap organization: Department of Bacterial and Parasitic Diseases, Armed Forces Research Institute of Medical Sciences – sequence: 23 givenname: David L. surname: Saunders fullname: Saunders, David L. organization: Department of Bacterial and Parasitic Diseases, Armed Forces Research Institute of Medical Sciences, Present address: Warfighter Expeditionary Medicine and Treatment, US Army Medical Material Development Activity – sequence: 24 givenname: Marcelo U. surname: Ferreira fullname: Ferreira, Marcelo U. organization: Department of Parasitology, Institute of Biomedical Sciences, University of São Paulo – sequence: 25 givenname: Myaing M. surname: Nyunt fullname: Nyunt, Myaing M. organization: Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Present address: Duke Global Health Institute, Duke University – sequence: 26 givenname: Miriam K. surname: Laufer fullname: Laufer, Miriam K. organization: Center for Vaccine Development and Global Health, University of Maryland School of Medicine – sequence: 27 givenname: Mark A. surname: Travassos fullname: Travassos, Mark A. organization: Center for Vaccine Development and Global Health, University of Maryland School of Medicine – sequence: 28 givenname: Robert W. surname: Sauerwein fullname: Sauerwein, Robert W. organization: Department of Medical Microbiology, Radboud University Medical Center – sequence: 29 givenname: Shannon surname: Takala-Harrison fullname: Takala-Harrison, Shannon organization: Center for Vaccine Development and Global Health, University of Maryland School of Medicine – sequence: 30 givenname: Claire M. surname: Fraser fullname: Fraser, Claire M. organization: Institute for Genome Sciences, University of Maryland School of Medicine – sequence: 31 givenname: B. Kim Lee surname: Sim fullname: Sim, B. Kim Lee organization: Sanaria, Inc – sequence: 32 givenname: Stephen L. surname: Hoffman fullname: Hoffman, Stephen L. organization: Sanaria, Inc – sequence: 33 givenname: Christopher V. surname: Plowe fullname: Plowe, Christopher V. organization: Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Present address: Duke Global Health Institute, Duke University – sequence: 34 givenname: Joana C. orcidid: 0000-0001-6502-7026 surname: Silva fullname: Silva, Joana C. email: jcsilva@som.umaryland.edu organization: Institute for Genome Sciences, University of Maryland School of Medicine, Department of Microbiology and Immunology, University of Maryland School of Medicine |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/31915075$$D View this record in MEDLINE/PubMed |
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Plasmodium falciparum
(Pf) whole-organism sporozoite vaccines have been shown to provide significant protection against controlled human malaria... Plasmodium falciparum (Pf) whole-organism sporozoite vaccines have been shown to provide significant protection against controlled human malaria infection... Background Plasmodium falciparum (Pf) whole-organism sporozoite vaccines have been shown to provide significant protection against controlled human malaria... Abstract Background Plasmodium falciparum (Pf) whole-organism sporozoite vaccines have been shown to provide significant protection against controlled human... |
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| SubjectTerms | Analysis Antigenic determinants Antigens Artemisinin Bioinformatics Biomedical and Life Sciences Biomedicine Cancer Research CD8 antigen CD8-Positive T-Lymphocytes - immunology Cell culture Clinical isolates Clinical trials Clinical Trials as Topic - statistics & numerical data Cloning Deoxyribonucleic acid DNA DNA binding proteins DNA sequencing Epitopes Erythrocytes Gene expression Genetic aspects Genetic engineering Genome assembly Genome, Protozoan Genomes Genomics Health aspects Human Genetics Humans Immunogenicity Immunogenicity, Vaccine Immunology Infection Infections Lymphocytes T Malaria Malaria Vaccines - genetics Malaria Vaccines - immunology Medical research Medicine/Public Health Metabolomics Mortality Nucleotide sequence P. falciparum Parasites PfSPZ vaccine Plasmodium falciparum Plasmodium falciparum - genetics Plasmodium falciparum - immunology Polymorphism, Genetic Product development Single-nucleotide polymorphism Strains (organisms) Structure (Literature) Systems Biology T cells Transcription factors Vaccine efficacy Vaccines Whole genome sequencing Whole-sporozoite vaccine |
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| Title | Strains used in whole organism Plasmodium falciparum vaccine trials differ in genome structure, sequence, and immunogenic potential |
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