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Engineering and characterization of a novel Self Assembling Protein for Toxoplasma peptide vaccine in HLA-A11:01, HLA-A02:01 and HLA-B*07:02 transgenic mice.

ABSTRACT: Fighting smart diseases requires smart vaccines. Novel ways to present protective immunogenic peptide epitopes to human immune systems are needed. Herein, we focus on Self Assembling Protein Nanoparticles (SAPNs) as scaffolds/platforms for vaccine delivery that produce strong immune responses against Toxoplasma gondii in HLA supermotif, transgenic mice. Herein, we present a useful platform to present peptides that elicit CD4+, CD8+ T and B cell immune responses in a core architecture, formed by flagellin, administered in combination with TLR4 ligand-emulsion (GLA-SE) adjuvant. We demonstrate protection of HLA-A*11:01, HLA-A*02:01, and HLA-B*07:02 mice against toxoplasmosis by (i) this novel chimeric polypeptide, containing epitopes that elicit CD8+ T cells, CD4+ T helper cells, and IgG2b antibodies, and (ii) adjuvant activation of innate immune TLR4 and TLR5 pathways. HLA-A*11:01, HLA-A*02:01, and HLA-B*07:02q11 transgenic mouse splenocytes with peptides demonstrated predicted genetic restrictions. This creates a new paradigm-shifting vaccine approach to prevent toxoplasmosis, extendable to other diseases.

SUBMITTER: El Bissati K

PROVIDER: S-EPMC7552409 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Engineering and characterization of a novel Self Assembling Protein for Toxoplasma peptide vaccine in HLA-A11:01, HLA-A02:01 and HLA-B*07:02 transgenic mice.

El Bissati Kamal K Zhou Ying Y Paulillo Sara M SM Raman Senthil K SK Karch Christopher P CP Reed Steve S Estes Ashley A Estes Amber A Lykins Joseph J Burkhard Peter P McLeod Rima R

Scientific reports 20201012 1

Fighting smart diseases requires smart vaccines. Novel ways to present protective immunogenic peptide epitopes to human immune systems are needed. Herein, we focus on Self Assembling Protein Nanoparticles (SAPNs) as scaffolds/platforms for vaccine delivery that produce strong immune responses against Toxoplasma gondii in HLA supermotif, transgenic mice. Herein, we present a useful platform to present peptides that elicit CD4<sup>+</sup>, CD8<sup>+</sup> T and B cell immune responses in a core ar ...[more]

PMID: 33046728

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Project description:Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus causing coronavirus disease 2019 (COVID-19) was announced as an outbreak by the World Health Organization (WHO) in January 2020 and as a pandemic in March 2020. The majority of infected individuals have experienced no or only mild symptoms, ranging from fully asymptomatic cases to mild pneumonic disease. However, a minority of infected individuals develop severe respiratory symptoms. The objective of this study was to identify susceptible HLA alleles and clinical markers that can be used in risk prediction model for the early identification of severe COVID-19 among hospitalized COVID-19 patients. A total of 137 patients with mild COVID-19 (mCOVID-19) and 53 patients with severe COVID-19 (sCOVID-19) were recruited from the Center Hospital of the National Center for Global Health and Medicine (NCGM), Tokyo, Japan for the period of February-August 2020. High-resolution sequencing-based typing for eight HLA genes was performed using next-generation sequencing. In the HLA association studies, HLA-A*11:01:01:01 [Pc = 0.013, OR = 2.26 (1.27-3.91)] and HLA-C*12:02:02:01-HLA-B*52:01:01:02 [Pc = 0.020, OR = 2.25 (1.24-3.92)] were found to be significantly associated with the severity of COVID-19. After multivariate analysis controlling for other confounding factors and comorbidities, HLA-A*11:01:01:01 [P = 3.34E-03, OR = 3.41 (1.50-7.73)], age at diagnosis [P = 1.29E-02, OR = 1.04 (1.01-1.07)] and sex at birth [P = 8.88E-03, OR = 2.92 (1.31-6.54)] remained significant. The area under the curve of the risk prediction model utilizing HLA-A*11:01:01:01, age at diagnosis, and sex at birth was 0.772, with sensitivity of 0.715 and specificity of 0.717. To the best of our knowledge, this is the first article that describes associations of HLA alleles with COVID-19 at the 4-field (highest) resolution level. Early identification of potential sCOVID-19 could help clinicians prioritize medical utility and significantly decrease mortality from COVID-19.

Dataset Information

Engineering and characterization of a novel Self Assembling Protein for Toxoplasma peptide vaccine in HLA-A11:01, HLA-A02:01 and HLA-B*07:02 transgenic mice.

Publications

Engineering and characterization of a novel Self Assembling Protein for Toxoplasma peptide vaccine in HLA-A11:01, HLA-A02:01 and HLA-B*07:02 transgenic mice.

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Dataset Information

Engineering and characterization of a novel Self Assembling Protein for Toxoplasma peptide vaccine in HLA-A*11:01, HLA-A*02:01 and HLA-B*07:02 transgenic mice.

Publications

Engineering and characterization of a novel Self Assembling Protein for Toxoplasma peptide vaccine in HLA-A*11:01, HLA-A*02:01 and HLA-B*07:02 transgenic mice.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Engineering and characterization of a novel Self Assembling Protein for Toxoplasma peptide vaccine in HLA-A11:01, HLA-A02:01 and HLA-B*07:02 transgenic mice.

Engineering and characterization of a novel Self Assembling Protein for Toxoplasma peptide vaccine in HLA-A11:01, HLA-A02:01 and HLA-B*07:02 transgenic mice.