Predictive Markers of Immunogenicity and Efficacy for Human Vaccines

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.

Keywords: high-throughput technologies; in vivo imaging; machine learning; preclinical models; predictive biomarkers; systems immunology; unsupervised analyses; vaccine signatures; vaccines.

Figure 1

Vaccine efficacy and safety are determined by interactions between innate and adaptive immunity. These interactions are shaped by host factors and can be orientated by vaccine properties.

Figure 2

From individuals to single cells: integrating multi-level data into comprehensive vaccine signatures. Host factors and vaccine properties are important determinants of immune responses. Variations of these determinants, such as genetic polymorphisms, age, host microbiome or immunization procedure, thus condition the definition of vaccine signatures. Systems immunology enables the identification of biomarkers of vaccine responses at multiple scales, from whole-body to cellular factors. Diverse high-throughput technologies, including in vivo imaging, allow the characterization of vaccine immune signatures through various applications, such as immune-cell tracking, cell immunophenotyping, and multiplex profiling. 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 HIV-1 envelope glycoprotein trimers in lymph nodes by immunohistofluorescence (IHF) [45].