Structural analysis of owl monkey MHC-DR shows that fully-protective malaria vaccine components can be readily used in humans

More than 50 years ago the owl monkey (genus Aotus) was found to be highly susceptible to developing human malaria, making it an excellent experimental model for this disease. Microbes and parasites' (especially malaria) tremendous genetic variability became resolved during our malaria vaccine...

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Autores:
Tipo de recurso:
Fecha de publicación:
2017
Institución:
Universidad del Rosario
Repositorio:
Repositorio EdocUR - U. Rosario
Idioma:
eng
OAI Identifier:
oai:repository.urosario.edu.co:10336/23518
Acceso en línea:
https://doi.org/10.1016/j.bbrc.2017.08.012
https://repository.urosario.edu.co/handle/10336/23518
Palabra clave:
HLA DRB1 antigen
Malaria vaccine
HLA antigen class 2
Malaria vaccine
Aotus
Article
Controlled study
Genetic variability
Human
Hydrophobicity
Immunofluorescence test
Immunogenicity
Malaria falciparum
Nonhuman
Plasmodium falciparum
Priority journal
Proton nuclear magnetic resonance
Static electricity
Vaccination
Western blotting
Animal
Antigen antibody reaction
Aotidae
Chemistry
Immunology
Animals
Antigen-Antibody Reactions
Aotidae
Histocompatibility Antigens Class II
Humans
Malaria Vaccines
Animal model
HLA-peptide binding
IMPIPS
Malarial-vaccine
MHC-DR
Rights
License
Abierto (Texto Completo)
Description
Summary:More than 50 years ago the owl monkey (genus Aotus) was found to be highly susceptible to developing human malaria, making it an excellent experimental model for this disease. Microbes and parasites' (especially malaria) tremendous genetic variability became resolved during our malaria vaccine development, involving conserved peptides having high host cell binding activity (cHABPs); however, cHABPs are immunologically silent and must be specially modified (mHABPs) to induce a perfect fit into major histocompatibility complex (MHC) molecules (HLA in humans). Since malarial immunity is mainly antibody-mediated and controlled by the HLA-DRB genetic region, ?1000 Aotus have been molecularly characterised for MHC-DRB, revealing striking similarity between human and Aotus MHC-DRB repertories. Such convergence suggested that a large group of immune protection-inducing protein structures (IMPIPS), highly immunogenic and protection inducers against malarial intravenous challenge in Aotus, could easily be used in humans for inducing full protection against malaria. We highlight the value of a logical and rational methodology for developing a vaccine in an appropriate animal model: Aotus monkeys. © 2017 Elsevier Inc.