Biology subjects

Carrington, C. V. F.

Publications and source records attributed to Carrington, C. V. F..

3 recordsLinked to original sources

bioRxiv2026

Tracking two decades of global dengue virus lineage dynamics

Dengue virus (DENV) is genetically diverse, consisting of four antigenically distinct serotypes and extensive sub-serotype variation that can influence epidemiology and control. As DENV continues to expand globally, there is an urgent need to characterize the dynamics of distinct DENV genetic lineages, including their persistence, establishment, and spread. Using a standardized DENV lineage nomenclature system and 37,828 publicly available DENV genomes sampled from 2000-2024, we classified sequences across nine global regions to construct a comprehensive resource of regional lineage distributions over time. We found marked regional differences in lineage diversity, with higher lineage richness in Southeast and East Asia than in the Americas. We further showed that COVID-19-related disruptions were associated with decreased regional lineage persistence and detection of new lineages during 2020-2021, followed by rebounds after 2022 and, in some regions, substantial lineage turnover. Finally, we identified a small set of globally expansive (cosmopolitan) lineages that are over-represented in available sequences, including five first-order minor lineages detected in at least seven of nine regions: 3III_B.3, 2II_F.1, 2II_A.1, 1III_A.3, and 1I_K.3. Together, these results demonstrate how standardized lineage classification enables global tracking of emerging DENV diversity and supports targeted genomic surveillance.

bioinformatics↗

bioRxiv2024

Population genetics, phylogeography and gene flow of mainland and island vampire bat (Desmodus rotundus) populations: an investigation into mainland-island bat movement

Movement of animals and plants from mainland populations contributes to the genetic diversity and viability of geographically isolated island biota, but also carries risks of pathogen introductions. The bat fauna of the island of Trinidad reflects species diversity on the neighbouring South American mainland and includes the common vampire bat (Desmodus rotundus). We determined relationships between Trinidad and mainland vampire bat populations and the extent of mainland-island movement by comparing the genetic structure (nuclear and mitochondrial) and morphology of the Trinidadian D. rotundus population to populations in neighbouring regions of the South American mainland and estimating evolutionary histories and patterns of gene flow. Results indicate that Trinidadian D. rotundus are genetically and morphologically distinct from mainland populations, although limited unidirectional male-biased mainland to island gene flow occurs at an estimated rate of 3.3 migrants per year. Two geographically-defined Desmodus cytochrome b clades were identified within Trinidad (i.e., one restricted to the South-Western peninsula which grouped with Venezuelan sequences and the other found throughout the rest of the island which grouped with sequences from Suriname and Guyana) suggesting long-standing female philopatry. The geographic distribution of these clades mirrors that of two previously identified geographically defined rabies virus (RABV) lineages introduced to Trinidad from the mainland. This finding suggests that bat dispersals and RABV introductions occur via both the northern and south-western island peninsulas, with subsequent male-driven intra-island viral spread enabled by bat nuclear homogeneity of these populations. These study findings will contribute to the development of contemporary evidence-based vampire bat population control and rabies prevention programs within island populations.

evolutionary biology↗

bioRxiv2020

Capturing and Recreating Diverse Antibody Repertoires as Multivalent Recombinant Polyclonal Antibody Drugs

Plasma-derived polyclonal antibodies are polyvalent drugs used for many important clinical indications that require modulation of multiple drug targets simultaneously, including emerging infectious disease and transplantation. However, plasma-derived drugs suffer many problems, including low potency, impurities, constraints on supply, and batch-to-batch variation. In this study, we demonstrated proofs-of-concept for a technology that uses microfluidics and molecular genomics to capture diverse mammalian antibody repertoires as multivalent recombinant drugs. These "recombinant hyperimmune" drugs comprised thousands to tens of thousands of antibodies and were derived from convalescent human donors, or vaccinated human donors or immunized mice. Here we used our technology to build a highly potent recombinant hyperimmune for Severe Acute Respiratory Syndrome Coronavirus-2 (SARS CoV-2) in less than three months. We also validated a recombinant hyperimmune for Zika virus disease that abrogates antibody-dependent enhancement (ADE) through Fc engineering. For patients with primary immune deficiency (PID), we built high potency polyvalent recombinant hyperimmunes against pathogens that commonly cause serious lung infections. Finally, to address the limitations of rabbit-derived anti-thymocyte globulin (ATG), we generated a recombinant human version and demonstrated in vivo function against graft-versus-host disease (GVHD). Recombinant hyperimmunes are a novel class of drugs that could be used to target a wide variety of other clinical applications, including cancer and autoimmunity.

immunology↗