Yonsei Med J.  2018 Mar;59(2):176-186. 10.3349/ymj.2018.59.2.176.

Systems Biology-Based Platforms to Accelerate Research of Emerging Infectious Diseases

• Oh SJ
• Choi YK
• Shin OS

• KMID: 2418779
• DOI: http://doi.org/10.3349/ymj.2018.59.2.176

Abstract

Emerging infectious diseases (EIDs) pose a major threat to public health and security. Given the dynamic nature and significant impact of EIDs, the most effective way to prevent and protect against them is to develop vaccines in advance. Systems biology approaches provide an integrative way to understand the complex immune response to pathogens. They can lead to a greater understanding of EID pathogenesis and facilitate the evaluation of newly developed vaccine-induced immunity in a timely manner. In recent years, advances in high throughput technologies have enabled researchers to successfully apply systems biology methods to analyze immune responses to a variety of pathogens and vaccines. Despite recent advances, computational and biological challenges impede wider application of systems biology approaches. This review highlights recent advances in the fields of systems immunology and vaccinology, and presents ways that systems biology-based platforms can be applied to accelerate a deeper understanding of the molecular mechanisms of immunity against EIDs.

Keyword

Emerging infectious diseases; systems biology; systems vaccinology; vaccines; immunity

MeSH Terms

*Communicable Diseases, Emerging
Humans
*Immunity
Research
Systems Biology/*methods
Vaccines/*immunology
Vaccines

Figure

• 

  Fig. 1 The process of systems vaccinology approaches. Systems biology approaches applied to clinical trials can lead to the generation of new hypotheses that can be tested and ultimately lead to better vaccine development. For example, correlates of vaccine-induced immunity in clinical trials can be profiled in detail with high-throughput technologies, such as RNA-sequencing, proteomics, and metabolomics. The high-throughput data thus generated can be integrated using bioinformatics tools and used to create hypotheses about the biological mechanisms underlying vaccine efficacy and immunogenicity. Such hypotheses can then be tested with animal models or in vitro human systems. The insights gained from experimentation can then guide the identification of biomarker and the design and development of new vaccines. Thus, systems vaccinology approaches can provide translational solutions for novel and enhanced vaccine development.

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  Fig. 2 Potential biases for systems vaccinology data analysis. The application of systems biology approaches to the fields of immunology and vaccinology faces many challenges and potential limitations. The potentially challenging factors for systems vaccinology analysis can be divided into different categories, such as cellular, population, molecular, individual, and technical aspects.

• 

  Fig. 3 Use of reverse vaccinology tools in vaccine design. The workflow of vaccine design using reverse vaccinology is shown. First, B cells or plasma cells can be isolated from infected or vaccinated individuals and PCR amplification of antibody gene heavy and light chains can lead to human B cell repertoire analysis, which enables the identification of protective antibodies. Using sequence information of antibody variable regions, the interaction of antibodies with their target antigen can be structurally characterized and used to predict the protective epitope using crystallography. The protective epitope can then be engineered to produce an optimized immunogen with enhanced delivery format, such as nanoparticle technologies or adjuvants. Finally, this new reverse vaccinology-based antigen can be tested in humans.

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