Dataset Information

Immunoinformatic construction of an adenovirus-based modular vaccine platform and its application in the design of a SARS-CoV-2 vaccine.

ABSTRACT: The current SARS-CoV-2 pandemic has imposed new challenges and demands for health systems, especially in the development of new vaccine strategies. Vaccines for many pathogens were developed based on the display of foreign epitopes in the variable regions of the human adenovirus (HAdV) major capsid proteins (hexon, penton and fiber). The humoral immune response against the HAdV major capsid proteins was demonstrated to play a role in the development of an immune response against the epitopes in display. Through the immunoinformatic profiling of the major capsid proteins of HAdVs from different species, we developed a modular concept that can be used in the development of vaccines based on HAdV vectors. Our data suggests that different immunomodulatory potentials can be observed in the conserved regions, present in the hexon and penton proteins, from different species. Using this modular approach, we developed a HAdV-5 based vaccine strategy for SARS-CoV-2, constructed through the display of SARS-CoV-2 epitopes indicated by our prediction analysis as immunologically relevant. The sequences of the HAdV vector major capsid proteins were also edited to enhance the IFN-gamma induction and antigen presenting cells activation. This is the first study proposing a modular HAdV platform developed to aid the design of new vaccines by inducing an immune response more suited for the epitopes in display.

SUBMITTER: Porto PS

PROVIDER: S-EPMC7833690 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Immunoinformatic construction of an adenovirus-based modular vaccine platform and its application in the design of a SARS-CoV-2 vaccine.

Porto Pedro Soares PS Anjos Déborah D Dábilla Nathânia N da Fonseca Simone Gonçalves SG Souza Menira M

Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases 20200803

The current SARS-CoV-2 pandemic has imposed new challenges and demands for health systems, especially in the development of new vaccine strategies. Vaccines for many pathogens were developed based on the display of foreign epitopes in the variable regions of the human adenovirus (HAdV) major capsid proteins (hexon, penton and fiber). The humoral immune response against the HAdV major capsid proteins was demonstrated to play a role in the development of an immune response against the epitopes in ...[more]

PMID: 32758675

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Project description:New universal prophylactic vaccine platforms are needed to prevent or reduce the impact of future respiratory viral infections. While the attribute of T memory cells is particularly attractive in the context of vaccine design for viral infection, the efficiency of T and B memory cell-mediated protection generated under the adenoviral vector was tested. We studied the mechanism using the platform/ immunological factor combination (AdV1+rRBD): adenovirus AdV1 (adjuvant) armed with inducible co-stimulator ICOS and CD40 ligand in combination with recombinant spike protein rRBD (antigen) to promote the differentiation of memory T and B cells. Additionally, adenovirus AdV2 (adjuvant) without ICOS and CD40 ligand in combination with rRBD was tested. Investigating ex vivo T cell responses to the platform-specific stimuli, we found higher frequencies of CD8+ than CD4+ platform-specific T cells vs mock. The cytometric analysis showed that T cells confer protection against SARS-CoV-2 via elevated T cell subsets: CD8+TEMRA (57.6% ± SD 3.3 vs mock 39.6% ± SD 4.83) and CD4+TNAÏVE (59.6% ± SD 0.4 vs mock 50.8% ± SD 1.9). We found that CD8+TEM, CD8+TSCM, and CD8+TCM are antigen-experienced subpopulations generated via the platform after 7 days. When stimulated with the immunological factors, B cells changed from the production of IgM and IgD to isotype IgG. The CD40 gene was significantly expressed (RT-qPCR) in VERO E6 after stimulation with the platform. RNA-seq profiling identified Th1, Th2, and Th17 cell differentiation gene expression patterns that effectively protect against different pathogens. RNA-seq analysis determined signaling pathways that control immunological mechanisms by which the platform induces protective immunity: MAPK cascade, adipocytokine, cAMP, TNF, and Toll-like receptor (TLR) signaling pathway. The formulation (AdV1+rRBD) increased the production of IL-6, IL-8, and TNF vs the mock (P<0.0001). The whole-genome sequencing of VERO E6 showed differences in the expression of apoptosis gene stimulated with the platforms vs mock. Moreover, apoptotic hallmarks were identified and quantified using flow cytometry. We proved that immunogenic factors compromised plasma membrane integrity (RNA-seq). To sum up, the proposed adenoviral platform generated innate and adaptive immunity for the complex and robust regulatory system to prevent SARS-CoV-2 infections.

Dataset Information

Immunoinformatic construction of an adenovirus-based modular vaccine platform and its application in the design of a SARS-CoV-2 vaccine.

Publications

Immunoinformatic construction of an adenovirus-based modular vaccine platform and its application in the design of a SARS-CoV-2 vaccine.

Similar Datasets

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