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Carrington, C. V. F.

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

2 recordsLinked to original sources

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↗

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↗