Abstract

Vaccines represent one of the major advances of modern medicine. Despite the many successes of vaccination, continuous efforts to design new vaccines are needed to fight “old” pandemics, such as tuberculosis and malaria, as well as emerging pathogens, such as Zika virus and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Vaccination aims at reaching sterilizing immunity, however assessing vaccine efficacy is still challenging and underscores the need for a better understanding of immune protective responses. Identifying reliable predictive markers of immunogenicity can help to select and develop promising vaccine candidates during early preclinical studies and can lead to improved, personalized, vaccination strategies. A systems biology approach is increasingly being adopted to address these major challenges using multiple high-dimensional technologies combined with in silico models. Although the goal is to develop predictive models of vaccine efficacy in humans, applying this approach to animal models empowers basic and translational vaccine research. In this review, we provide an overview of vaccine immune signatures in preclinical models, as well as in target human populations. We also discuss high-throughput technologies used to probe vaccine-induced responses, along with data analysis and computational methodologies applied to the predictive modeling of vaccine efficacy.

Highlights

  • Vaccines are the most effective preventive measure ever developed in the fight against diseases

  • Combining and integrating data at different scales will be of great value in identifying extensive vaccine immune signatures. (a) Positron emission tomography-computed tomography (PET-CT) imaging of the yellow fever (YF) preM mRNA vaccine in non-human primates (NHPs) [41]. (b) Near-infrared fluorescence (NIR) imaging to follow an anti-Langerin-HIVGag fusion vaccine from the injection site to the draining lymph node [42]. (c) Magnetic resonance imaging (MRI) of a dendritic cells (DCs)-based vaccine in the lymph node [43]. (d) In vivo tracking of Langerhans cells within the skin by fibered confocal fluorescence microscopy (FCFM)

  • Combining and integrating data at different scales will be of great value in identifying extensive vaccine immune signatures. (a) Positron emission tomography-computed tomography (PET-CT) imaging of the YF preM mRNA vaccine in NHPs [41]. (b) Near-infrared fluorescence (NIR) imaging to follow an anti-Langerin-HIVGag fusion vaccine from the injection site to the draining lymph node [42]. (c) Magnetic resonance imaging (MRI) of a DC-based vaccine in the lymph node [43]. (d) In vivo tracking of Langerhans cells within the skin by fibered confocal fluorescence microscopy (FCFM) [44]. (e) Tracking of fluorescently labeled human immunodeficiency virus (HIV)-1 envelope glycoprotein trimers in lymph nodes by immunohistofluorescence (IHF) [45]

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Summary

Introduction

Vaccines are the most effective preventive measure ever developed in the fight against diseases. The emerging field of systems vaccinology aims to identify biomarkers and immune signatures that correlate with vaccine efficacy to decipher protective immune mechanisms. High-throughput technologies have rapidly expanded over the last several years and have been frequently employed in systems vaccinology studies, making it possible to extend the range of biomarkers included in vaccine signatures [8,9,10,11,12]. New approaches in data analysis methodologies and computational modeling take vaccine signatures a step further by giving rise to the possibility of identifying immune responses that correlate and/or predict vaccine efficacy. Systems vaccinology aims to develop predictive models of vaccine efficacy in human populations, applying the same approach to animal models, which allow the use of a wide range of tools in controlled study designs, empowers vaccine research and improves preclinical studies. We present data analysis and computational methodologies used to define signatures that correlate with and potentially predict vaccine efficacy

Identification of Biomarkers and Signatures of Vaccine Responses
From What Samples Can We Identify Vaccine Response Biomarkers?
At What Time Should We Identify Vaccine Response Biomarkers?
Cytokine Profiling
OMICS Technologies
Whole Body Imaging of Vaccine Distribution and the Immune Response
Ex Vivo Multiparametric Analyses
Machine Learning and In Silico Models
Defining New Correlates of Protection
Stepping up Personalized Vaccinology
Improving Vaccine Formulation and Administration
Deciphering Mechanisms That Underly Immune Protective Responses
Findings
Conclusions
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