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Functional Comparison of Blood-Stage Plasmodium falciparum Malaria Vaccine Candidate Antigens.

Joseph J Illingworth | Daniel G Alanine | Rebecca Brown | Jennifer M Marshall | Helen E Bartlett | Sarah E Silk | Geneviève M Labbé | Doris Quinkert | Jee Sun Cho | Jason P Wendler | David J Pattinson | Lea Barfod | Alexander D Douglas | Michael W Shea | Katherine E Wright | Simone C de Cassan | Matthew K Higgins | Simon J Draper
Frontiers in immunology | 2019

The malaria genome encodes over 5,000 proteins and many of these have also been proposed to be potential vaccine candidates, although few of these have been tested clinically. RH5 is one of the leading blood-stage Plasmodium falciparum malaria vaccine antigens and Phase I/II clinical trials of vaccines containing this antigen are currently underway. Its likely mechanism of action is to elicit antibodies that can neutralize merozoites by blocking their invasion of red blood cells (RBC). However, many other antigens could also elicit neutralizing antibodies against the merozoite, and most of these have never been compared directly to RH5. The objective of this study was to compare a range of blood-stage antigens to RH5, to identify any antigens that outperform or synergize with anti-RH5 antibodies. We selected 55 gene products, covering 15 candidate antigens that have been described in the literature and 40 genes selected on the basis of bioinformatics functional prediction. We were able to make 20 protein-in-adjuvant vaccines from the original selection. Of these, S-antigen and CyRPA robustly elicited antibodies with neutralizing properties. Anti-CyRPA IgG generally showed additive GIA with anti-RH5 IgG, although high levels of anti-CyRPA-specific rabbit polyclonal IgG were required to achieve 50% GIA. Our data suggest that further vaccine antigen screening efforts are required to identify a second merozoite target with similar antibody-susceptibility to RH5.

Pubmed ID: 31214195

Associated grants

  • Agency: Wellcome Trust, United Kingdom
    Id: 201477/Z/16/Z
  • Agency: Wellcome Trust, United Kingdom
    Id: 106917/Z/15/Z
  • Agency: Wellcome Trust, United Kingdom
  • Agency: Wellcome Trust, United Kingdom
    Id: 101020/Z/13/Z
  • Agency: Wellcome Trust, United Kingdom
    Id: 105399/Z/14/Z

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This is a list of tools and resources that we have found mentioned in this publication.


BacPac Resources Center (tool)

RRID:SCR_001520

It is the distribution arm of their academic laboratory. They operate on a cost-recovery mechanism in order to make the resources generated in their laboratory available to the academic scientific community. While clones and screening services are widely available, library arrays are primarily available to researchers with a scientific need to analyze most clones in the library. This site contains information on currently available BAC and PAC genomic DNA libraries, BAC Clones, PAC Clones, Fosmid Clones, cDNA collections, high-density colony hybridization filters, and BAC and PAC cloning vectors. Protocols used in our laboratory for the hybridization-based screening of colony filters, purification of BAC and PAC DNA, and end-sequencing methodologies, are also provided. BPRC does not list clones, for two reasons: 1)most clones have not been characterized and lack specific data. 2)all clones are part of libraries and all clones from a particular library share common characteristics. Hence, to find out if BPRC has a particular clone, one needs either use Automatic Clone Validation or else find out if the clone is compatible with the range of clone names for a corresponding clone library. Typically (although not always), clone names are derived from the library name. BPRC uses the NCBI-recommended clone nomenclature & library nomenclature. Most arrayed libraries are available in frozen microtiter dish format to academic and non-academic users provided that there is a scientific need for complete-library access. (for instance to annotate, modify or analyze all BAC clones as part of a genome project).

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NetNGlyc (tool)

RRID:SCR_001570

Server that predicts N-Glycosylation sites in human proteins using artificial neural networks that examine the sequence context of Asn-Xaa-Ser/Thr sequons. NetNGlyc 1.0 is also available as a stand-alone software package, with the same functionality as the service above. Ready-to-ship packages exist for the most common UNIX platforms.

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GraphPad Prism (tool)

RRID:SCR_002798

Statistical analysis software that combines scientific graphing, comprehensive curve fitting (nonlinear regression), understandable statistics, and data organization. Designed for biological research applications in pharmacology, physiology, and other biological fields for data analysis, hypothesis testing, and modeling.

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GenScript (tool)

RRID:SCR_002891

Commercial organization which provides life science services and products to researchers. They specialize in gene synthesis, peptide, protein, antibody and preclinical drug development service.

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Thermo Fisher Scientific (tool)

RRID:SCR_008452

Commercial vendor and service provider of laboratory reagents and antibodies. Supplier of scientific instrumentation, reagents and consumables, and software services.

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Millipore (tool)

RRID:SCR_008983

An Antibody supplier

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New England Biolabs (tool)

RRID:SCR_013517

An Antibody supplier

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BALB/cAnNCrl (tool)

RRID:MGI:2683685

laboratory mouse with name BALB/cAnNCrl from MGI.

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WI (tool)

RRID:RGD_13508588

Rattus norvegicus with name WI from RGD.

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SD (tool)

RRID:RGD_70508

Rattus norvegicus with name SD from RGD.

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HEK293 (tool)

RRID:CVCL_0045

Cell line HEK293 is a Transformed cell line with a species of origin Homo sapiens (Human)

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