Immunogenicity Testing in the Era of Reverse and Systems Vaccinology
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Keywords:Immunogenicity testing, ex vivo/in vivo methods, rational vaccine discovery, vaccine efficacy evaluation
Immunogenicity testing is an essential step in the preclinical phase of vaccine development and the quality control of commercial vaccines. This often employs protection of the host against pathogen challenge. Alternatively, ex vivo or in vitro measurement of immune parameters that correlate with protection may be done. Immune markers of infection, disease and vaccine-induced protection are being searched by employing modern approaches, including immunomics, computational immunology and systems vaccinology. Various humoral and cellular immune parameters are suggested as potential correlates or surrogates of protection induced by human and animal vaccines. Ex vivo and in vitro assays that measure immune cell proliferation, phenotypes, signaling, cytotoxicity, production of cytokines, antibodies, etc. provide an early and/or ethically improved readout of vaccine immunogenicity, thereby saving costs, time and animal suffering. Whole blood, peripheral blood mononuclear cells (PBMCs) or monocyte-derived dendritic cells (MoDCs)-co-cultured with PBMCs or T cell subsets can be used in these assays to examine primary or recall immune responses. In vitro antigen-primed MoDC: T cell co-culture models and artificial immune systems are being standardized and validated for evaluation of vaccine immunogens. The usefulness of immunogenicity testing â€˜outside animalsâ€™ is likely to increase in future, with its focus on measuring the correlates of protection or surrogates of B and T cell immunity, which are being established for increasing number of current and future vaccines in the era of â€˜reverseâ€™ and â€˜systemsâ€™ vaccinology.
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