Virome-wide detection of natural infection events and the associated antibody dynamics using longitudinal highly-multiplexed serology

Abstract

Current methods for detecting infections either require a sample collected from an actively infected site, are limited in the number of agents they can query, and/or yield no information on the immune response. Here we present an approach that uses temporally coordinated changes in highly-multiplexed antibody measurements from longitudinal blood samples to monitor infection events at sub-species resolution across the human virome. In a longitudinally-sampled cohort of South African adolescents representing >100 person-years, we identify >650 events across 48 virus species and observe strong epidemic effects, including high-incidence waves of Aichivirus A and the D68 subtype of Enterovirus D earlier than their widespread circulation was appreciated. In separate cohorts of adults who were sampled at higher frequency using self-collected dried blood spots, we show that such events temporally correlate with symptoms and transient inflammatory biomarker elevations, and observe the responding antibodies to persist for periods ranging from ≤1 week to >5 years. Our approach generates a rich view of viral/host dynamics, supporting novel studies in immunology and epidemiology.

What is the role of microbial biotechnology and genetic engineering in medicine?

“…Hundreds of species of viruses can infect humans, leading to outcomes ranging from asymptomatic seroconversion to severe diseases, which can include respiratory failure, neurological damage, or hemorrhage (Kelley et al, 2023 ). Viral diseases can be as benign as the common cold or as deadly as Ebola.…”

Mapping disparities in viral infection rates using highly-multiplexed serology

“…Recent advances in serological methods have overcome previous limitations in breadth and are enabling unprecedented views into the viral exposure histories of individuals (25)(26)(27)(28). Using current approaches for highly-multiplexed serology (e.g., PepSeq (29), PhIP-Seq (30)) it is now possible to characterize antibody binding to 100,000s of antigens in a single assay using <1 µL of blood.…”

Aichivirus A1 replicates in human intestinal epithelium and bronchial tissue: Lung–gut axis?

“…Compared to European or Asian countries, Tunisia reported a high number of infections and relatively high rates of hospitalisation in children due to AiV-A1, ranking it as the third most frequently detected agent after rotavirus and norovirus ( Sdiri-Loulizi et al, 2010 ). Along these lines, recently developed highly multiplexed antibody measurements on a population scale delineated high-prevalence epidemic waves for Aichivirus A, beside enterovirus D68 (EV-D68), in the summer of 2008 in South Africa ( Kelley et al, 2023 ).…”