Abstract
Emergence and re-emergence of pathogens bearing the risk of becoming a pandemic threat are on the rise. Increased travel and trade, growing population density, changes in urbanization, and climate have a critical impact on infectious disease spread. Currently, the world is confronted with the emergence of a novel coronavirus SARS-CoV-2, responsible for yet more than 800 000 deaths globally. Outbreaks caused by viruses, such as SARS-CoV-2, HIV, Ebola, influenza, and Zika, have increased over the past decade, underlining the need for a rapid development of diagnostics and vaccines. Hence, the rational identification of biomarkers for diagnostic measures on the one hand, and antigenic targets for vaccine development on the other, are of utmost importance. Peptide microarrays can display large numbers of putative target proteins translated into overlapping linear (and cyclic) peptides for a multiplexed, high-throughput antibody analysis. This enabled for example the identification of discriminant/diagnostic epitopes in Zika or influenza and mapping epitope evolution in natural infections versus vaccinations. In this review, we highlight synthesis platforms that facilitate fast and flexible generation of high-density peptide microarrays. We further outline the multifaceted applications of these peptide array platforms for the development of serological tests and vaccines to quickly encounter pandemic threats.
Highlights
In a pandemic situation, the outbreak of an infectious disease has spread globally with a major impact on morbidity and mortality
Peptide microarrays have been applied for many different infectious diseases
To give several examples of the extensive list, peptide arrays are employed to decipher epitope-specific antibody responses, to evaluate or map vaccine-induced immune responses, or to identify novel targets for vaccine development and diagnostics in (1) malaria,[122−133] (2) Lyme disease,[134−137] (3) schistosomiasis,[138] (4) Chagas disease,[139,140] (5) toxoplasmosis,[141−143] (6) Crimean-Congo hemorrhagic fever,[144,145] (7) tick-borne diseases,[137] and (8) tick-borne encephalitis.[58]
Summary
The outbreak of an infectious disease has spread globally with a major impact on morbidity and mortality. Peptide microarrays[11] are an ideal tool to decipher epitopespecific humoral immune responses toward the (full) proteome of an emerging pathogen (Figure 1) They enable the analysis of tens of thousands of peptides simultaneously in a fast and cost-effective way for applications, such as epitope mapping, diagnostics, epitope discrimination, vaccine development, and vaccine monitoring. ELISA, with the lowest number of possible parameters per sample (1 peptide per sample), is followed by bead-based multiplex systems (up to ∼500 peptides per sample),[20] peptide microarrays (typically 500−50 000 peptides per sample), and phage display (library size up to 109−1010).[12] Unique for the latter one is the generation of phage particles, expressing an unrivaled diversity of peptides It apparently has some inherent bias, since it is a biological workflow, prone to for example unspecific binding (e.g., the VirScan approach[14] did not identify a highly common polio virus epitope). We give an overview on their applications in the field of epidemic/pandemic infectious diseases, where parts or the full proteome of an emerging or mutated pathogen were screened, to quickly respond to a pandemic threat
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