Chapter 5
Antigen Discovery in Bacterial Panproteomes
Daniel Yero, Oscar Conchillo-Sole ´ , and Xavier Daura
Abstract
There is still a lack of vaccines for many bacterial infections for which the best treatment option would be a
prophylactic one. On the other hand, effectiveness has been questioned for some existing vaccines,
prompting new developments. Therapeutic vaccines are also becoming a treatment option in specific
cases where antibiotics tend to fail. In this scenario, refinement and extension of the classical reverse
vaccinology approach is allowing scientists to find new and more effective antigens. In this chapter, we
describe an in silico methodology that integrates pangenomic, immunoinformatic, structural, and evolutionary approaches for the screening of potential antigens in a given bacterial species. The strategy focuses
on targeting relatively conserved epitopes in core proteins to design broadly cross-protective vaccines and
avoid allele-specific immunity. The proposed methodological steps and computational tools can be easily
implemented in a reverse vaccinology approach not only to identify new leads with strong immune response
but also to develop diagnostic assays.
Key words Computational antigen discovery, Immunoinformatics, Bacteria, Vaccines
1 Introduction
Pathogen antigens are molecules or molecular complexes of a
pathogenic organism that are directly recognized by specific
immune system receptors (e.g., T-cell and B-cell receptors) or
secreted immunoglobulins and that may elicit a host immune
response. Not all antigens are competent immunogens or induce
a protective adaptive response. In fact some pathogens display
antigens whose objective is to misdirect or even suppress the host
immune response. The search for vaccine candidates is therefore
not a “simple” search for antigens but a search for antigens capable
of eliciting a protective memory immune response [1].
The availability of whole genome sequences and corresponding
proteomes for a diversity of strains of each of the main pathogenic
bacterial species promises to accelerate the identification of vaccine
candidates [2]. Thus, the discovery of protein antigens by computational methods is progressively more reliant on an integrated
analysis of the ever-increasing genomic and proteomic data. At
Blaine A. Pfeifer and Andrew Hill (eds.), Vaccine Delivery Technology: Methods and Protocols, Methods in Molecular Biology,
vol. 2183, https://doi.org/10.1007/978-1-0716-0795-4_5, © Springer Science+Business Media, LLC, part of Springer Nature 2021
43
Antigen Discovery in Bacterial Panproteomes
Daniel Yero, Oscar Conchillo-Sole ´ , and Xavier Daura
Abstract
There is still a lack of vaccines for many bacterial infections for which the best treatment option would be a
prophylactic one. On the other hand, effectiveness has been questioned for some existing vaccines,
prompting new developments. Therapeutic vaccines are also becoming a treatment option in specific
cases where antibiotics tend to fail. In this scenario, refinement and extension of the classical reverse
vaccinology approach is allowing scientists to find new and more effective antigens. In this chapter, we
describe an in silico methodology that integrates pangenomic, immunoinformatic, structural, and evolutionary approaches for the screening of potential antigens in a given bacterial species. The strategy focuses
on targeting relatively conserved epitopes in core proteins to design broadly cross-protective vaccines and
avoid allele-specific immunity. The proposed methodological steps and computational tools can be easily
implemented in a reverse vaccinology approach not only to identify new leads with strong immune response
but also to develop diagnostic assays.
Key words Computational antigen discovery, Immunoinformatics, Bacteria, Vaccines
1 Introduction
Pathogen antigens are molecules or molecular complexes of a
pathogenic organism that are directly recognized by specific
immune system receptors (e.g., T-cell and B-cell receptors) or
secreted immunoglobulins and that may elicit a host immune
response. Not all antigens are competent immunogens or induce
a protective adaptive response. In fact some pathogens display
antigens whose objective is to misdirect or even suppress the host
immune response. The search for vaccine candidates is therefore
not a “simple” search for antigens but a search for antigens capable
of eliciting a protective memory immune response [1].
The availability of whole genome sequences and corresponding
proteomes for a diversity of strains of each of the main pathogenic
bacterial species promises to accelerate the identification of vaccine
candidates [2]. Thus, the discovery of protein antigens by computational methods is progressively more reliant on an integrated
analysis of the ever-increasing genomic and proteomic data. At
Blaine A. Pfeifer and Andrew Hill (eds.), Vaccine Delivery Technology: Methods and Protocols, Methods in Molecular Biology,
vol. 2183, https://doi.org/10.1007/978-1-0716-0795-4_5, © Springer Science+Business Media, LLC, part of Springer Nature 2021
43