Utilizing Computational Machine Learning Tools to Understand Immunogenic Breadth in the Context of a CD8 T-Cell Mediated HIV Response

Predictive models are becoming more and more commonplace as tools for candidate antigen discovery to meet the challenges of enabling epitope mapping of cohorts with diverse HLA properties. Here we build on the concept of using two key parameters, diversity metric of the HLA profile of individuals wi...

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Detalles Bibliográficos
Autores: McGowan, Ed, Rosenthal, Rachel, Fiore Gartland, Andrew, Macharia, Gladys, Balinda, Sheila, Kapaata, Anne, Umviligihozo, Gisele, Muok, Erick, Dalel, Jama, Streatfield, Claire L., Coutinho, Helen, Dilernia, Dario, Monaco, Daniela C., Morrison, David, Yue, Ling, Hunter, Eric, Nielsen, Morten, Gilmour, Jill, Hare, Jonathan
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2021
País:Argentina
Institución:Consejo Nacional de Investigaciones Científicas y Técnicas
Repositorio:CONICET Digital (CONICET)
Idioma:inglés
OAI Identifier:oai:ri.conicet.gov.ar:11336/178451
Acceso en línea:http://hdl.handle.net/11336/178451
Access Level:acceso abierto
Palabra clave:CD8 T-CELLS
HIV
MACHINE LEARNING
T-CELL EPITOPES
VACCINES
https://purl.org/becyt/ford/3.3
https://purl.org/becyt/ford/3
Descripción
Sumario:Predictive models are becoming more and more commonplace as tools for candidate antigen discovery to meet the challenges of enabling epitope mapping of cohorts with diverse HLA properties. Here we build on the concept of using two key parameters, diversity metric of the HLA profile of individuals within a population and consideration of sequence diversity in the context of an individual's CD8 T-cell immune repertoire to assess the HIV proteome for defined regions of immunogenicity. Using this approach, analysis of HLA adaptation and functional immunogenicity data enabled the identification of regions within the proteome that offer significant conservation, HLA recognition within a population, low prevalence of HLA adaptation and demonstrated immunogenicity. We believe this unique and novel approach to vaccine design as a supplement to vitro functional assays, offers a bespoke pipeline for expedited and rational CD8 T-cell vaccine design for HIV and potentially other pathogens with the potential for both global and local coverage.

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