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Dear Colleagues,

Never has there been a more pertinent time to underline the importance of new vaccine development and rapid disease diagnosis. Structural vaccinology (SV) methods that combine high-resolution structural biology techniques with computational biology and immunological validation, can drive the design of better, protein-based vaccine components, endowed with improved biochemical and/or immunological properties. Among the many applications, structure-based antigen engineering can allow us to map epitope regions, block specific antigen conformations that induce pathogen-neutralizing antibodies or can permit us to define the boundaries of protective epitope containing regions/domains, for more facile, large scale production. Furthermore, the availability of antigen structures, alone and in antibody complexes, has fuelled the development of eloquent computational epitope prediction and antigen design methods that have achieved optimum levels of accuracy, representing essential tools for vaccine design. Vaccine components can have secondary uses as serological diagnostic markers that detect their cognate antibodies, induced in subjects with prior exposure to the related pathogen. Presentation of diagnostic epitopes or whole antigens belonging to different infection stages and diseases can spur the design of Multiplex diagnostic tests, capable of rapidly detecting multiple diseases and infection progress. Recent advances in single particle cryo-electron microscopy and the ability to solve the structures of larger, more complex antigen structures will inevitably provide an increased repertoire of available antigen (and antigen-antibody) structures; therefore, examples of SV are likely to increase in the near future. In this context, this Special Issue summarizes the current applications of Structural Vaccinology to both the design of novel therapeutics (vaccines) and diagnostics.

Prof. Louise J. Gourlay
Guest Editor

Manuscript Submission Information

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Keywords

Structure-based antigen engineering
vaccine design
epitope-based diagnostic biomarkers
structural vaccinology
protein antigens

Published Papers (2 papers)

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Research

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Open AccessArticle

Elucidating the 3D Structure of a Surface Membrane Antigen from Trypanosoma cruzi as a Serodiagnostic Biomarker of Chagas Disease

Vaccines 2022, 10(1), 71; https://doi.org/10.3390/vaccines10010071 - 03 Jan 2022

Viewed by 1427

Abstract

Chagas disease (CD) is a vector-borne parasitosis, caused by the protozoan parasite Trypanosoma cruzi, that affects millions of people worldwide. Although endemic in South America, CD is emerging throughout the world due to climate change and increased immigratory flux of infected people to non-endemic regions. Containing of the diffusion of CD is challenged by the asymptomatic nature of the disease in early infection stages and by the lack of a rapid and effective diagnostic test. With the aim of designing new serodiagnostic molecules to be implemented in a microarray-based diagnostic set-up for early screening of CD, herein, we report the recombinant production of the extracellular domain of a surface membrane antigen from T. cruzi (TcSMP) and confirm its ability to detect plasma antibodies from infected patients. Moreover, we describe its high-resolution (1.62 Å) crystal structure, to which in silico epitope predictions were applied in order to locate the most immunoreactive regions of TcSMP in order to guide the design of epitopes that may be used as an alternative to the full-length antigen for CD diagnosis. Two putative, linear epitopes, belonging to the same immunogenic region, were synthesized as free peptides, and their immunological properties were tested in vitro. Although both peptides were shown to adopt a structural conformation that allowed their recognition by polyclonal antibodies raised against the recombinant protein, they were not serodiagnostic for T. cruzi infections. Nevertheless, they represent good starting points for further iterative structure-based (re)design cycles. Full article

(This article belongs to the Special Issue Therapeutic and Diagnostic Applications of Structural Vaccinology)

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Review

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Open AccessReview

SARS-CoV-2–Specific Vaccine Candidates; the Contribution of Structural Vaccinology

Su Min Pack

and

Peter J. Peters

Vaccines 2022, 10(2), 236; https://doi.org/10.3390/vaccines10020236 - 03 Feb 2022

Cited by 11 | Viewed by 2060

Abstract

SARS-CoV-2 vaccine production has taken us by storm. We aim to fill in the history of concepts and the work of pioneers and provide a framework of strategies employing structural vaccinology. Cryo-electron microscopy became crucial in providing three-dimensional (3D) structures and creating candidates eliciting T and B cell-mediated immunity. It also determined structural changes in the emerging mutants in order to design new constructs that can be easily, quickly and safely added to the vaccines. The full-length spike (S) protein, the S1 subunit and its receptor binding domain (RBD) of the virus are the best candidates. The vaccine development to cease this COVID-19 pandemic sets a milestone for the pan-coronavirus vaccine’s designing and manufacturing. By employing structural vaccinology, we propose that the mRNA and the protein sequences of the currently approved vaccines should be modified rapidly to keep up with the more infectious new variants. Full article

(This article belongs to the Special Issue Therapeutic and Diagnostic Applications of Structural Vaccinology)

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