Meta‐analysis of immune epitope data for all <i>Plasmodia</i>: overview and applications for malarial immunobiology and vaccine‐related issues

Vaughan, Kerrie; Blythe, Martin; Greenbaum, Jason A.; Zhang, Q.; Peters, Bjoern; Doolan, Denise L.; Sette, Alessandro

doi:10.1111/j.1365-3024.2008.01077.x

Cited by 30 publications

(32 citation statements)

References 55 publications

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“…Hitherto the sequences of approximately 5300 proteins were annotated for Plasmodium falciparum genome . Among them, there were identified about 4500 unique epitopes (present in about 1500 proteins), which are short protein motifs recognized by the host immune system (Vaughan et al, 2009 These results shows that comparison between currently existing diversity and genome of P. reichenovi may reveal immune pressure acting on pathogen after the speciation.…”

Section: Introductionmentioning

confidence: 86%

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Analysis of immunogenicity of different protein groups from malaria parasite Plasmodium falciparum

Krzyczmonik

Świtnicki

Kaczanowski

2012

Infection, Genetics and Evolution

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It was observed that pressure of host immune system leads to diversifying selection (which can be measured in terms of pN/pS ratio). In this research we checked whether Plasmodium falciparum proteins containing experimentally evident epitopes from the IEDB database are subject to diversifying selection. We also investigated which life stage of this parasite and which proteins are subject to the strongest immune pressure. To answer these questions we used information about experimentally evident epitopes from Plasmodium, that interact with human immune system and sequences of different isolates of P. falciparum.We confirmed the expectations that proteins containing IEDB epitopes are subject to stronger diversifying selection which is evidenced by higher pN/pS ratio. A stage characterized by the highest average pN/pS ratio is that of the sporozoite. The greatest fraction of putative antigens is also present at this stage. We also found that the sporozoite stage is particularly interesting for further analysis as it potentially contains the highest number of unidentified epitopes.

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Section: Introductionmentioning

confidence: 86%

“…Due to the complexity of the life cycle, each life stage expresses a number of antigenic proteins that can induce an immune response and which presents a real challenge for vaccine design (Vaughan et al, 2009). …”

Section: Introductionmentioning

confidence: 99%

Analysis of immunogenicity of different protein groups from malaria parasite Plasmodium falciparum

Krzyczmonik

Świtnicki

Kaczanowski

2012

Infection, Genetics and Evolution

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“…Meta-analyses have been conducted for several highprofile pathogens, such as influenza A virus, mycobacteria (M. tuberculosis and related species), anthrax, and botulinum toxins, and all Plasmodium species (8,11,101,112). These analyses have provided comprehensive catalogs of pathogenspecific epitope data, and at the same time have identified critical knowledge gaps and highlighted potential areas for further research.…”

Section: Introductionmentioning

confidence: 98%

Meta-analysis of All Immune Epitope Data in theFlavivirusGenus: Inventory of Current Immune Epitope Data Status in the Context of Virus Immunity and Immunopathology

Vaughan

Greenbaum²,

Blythe³

et al. 2010

Viral Immunology

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A meta-analysis was performed in order to inventory the immune epitope data related to viruses in the genus Flavivirus. Nearly 2000 epitopes were captured from over 130 individual Flavivirus-related references identified from PubMed and reported as of September 2009. This report includes all epitope structures and associated immune reactivity from the past and current literature, including: the epitope distribution among pathogens and related strains, the epitope distribution among different pathogen antigens, the number of epitopes defined in human and animal models of disease, the relationship between epitopes identified in different disease states following natural (or experimental) infection, and data from studies focused on candidate vaccines. We found that the majority of epitopes were defined for dengue virus (DENV) and West Nile virus (WNV). The prominence of DENV and WNV data in the epitope literature is likely a reflection of their overall worldwide impact on human disease, and the lack of vaccines. Conversely, the relatively smaller number of epitopes defined for the other viruses within the genus (yellow fever and Japanese encephalitis virus) most likely reflects the presence of established prophylaxis and/or their more modest impact on morbidity and mortality globally. Through this work we hope to provide useful data to those working in the area of Flavivirus research.

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“…By conducting a comprehensive meta-analysis of available data for Plasmodium immune epitopes, Vaughan et al have identified more than 5,000 unique B-cell and T-cell epitopes for malaria parasites (60). Several of the P. falciparum and P. vivax epitopes were identified in extensive field studies conducted over the last 2 decades (12,23,35,57) and by computer-based predictions of immune epitopes by analysis of genomic and proteomic databases; some of these predictions were validated in HLA-peptide binding studies and in vitro immunological studies (4,(11)(12)(13)29).…”

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confidence: 99%

Multiple Antigen Peptide Vaccines againstPlasmodium falciparumMalaria

et al. 2010

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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). Vaccinations against several deadly infectious agents continue to save millions of lives annually and have improved the quality of life of tens of millions of individuals by significantly preventing or reducing the transmission of several pandemic and locally transmitted infectious diseases. Thus, there are reasons to believe that a successful malaria vaccine would not only significantly reduce malaria mortality and morbidity but also become an important tool in disease control efforts.The quest to develop a malaria vaccine began more than 6 decades ago with successful vaccination against malaria in birds (16). Since then, several decades of research in experimental models have demonstrated that both whole-parasiteand subunit (recombinant and synthetically produced)-based vaccines can induce protective immunity when delivered under optimal conditions. However, after hundreds of millions of dollars in investments and several dozen clinical trials, recombinant-protein-based candidate malaria vaccines have failed to induce the level of protection that would warrant production as licensed vaccines. The most successful recombinant vaccine, RTS,S, has undergone trials and, at its best, induced 53% protection against clinical malaria in a placebo-controlled clinical trial that involved 5-to 17-month-old children in Kenya and Tanzania (3). The limited success of recombinant vaccines has led to a surge in interest to produce and test whole attenuated parasite-based vaccines against malaria, most of which are based on live attenuated Plasmodium falciparum sporozoites (24, 59). Nonetheless, the whole-parasite-based vaccination approach presents unique challenges in terms of safety, residual virulence, and the potential for reversion in virulence, mode of delivery, and difficulties associated with sufficient production for en masse vaccination. Thus, given the limited amount of clinical immunity conferred by the recombinantprotein-based vaccines and the perceived hurdles with the whole-parasite-base...

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Meta‐analysis of immune epitope data for all Plasmodia: overview and applications for malarial immunobiology and vaccine‐related issues

Cited by 30 publications

References 55 publications

Analysis of immunogenicity of different protein groups from malaria parasite Plasmodium falciparum

Analysis of immunogenicity of different protein groups from malaria parasite Plasmodium falciparum

Meta-analysis of All Immune Epitope Data in theFlavivirusGenus: Inventory of Current Immune Epitope Data Status in the Context of Virus Immunity and Immunopathology

Multiple Antigen Peptide Vaccines againstPlasmodium falciparumMalaria

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