The bright and the dark side of human antibody responses to flaviviruses: lessons for vaccine design

Autor: Franz X. Heinz, Karin Stiasny, Marie-Christine Vaney, Félix A. Rey, Mariano Dellarole
Přispěvatelé: Virologie Structurale - Structural Virology, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Institute of Virology (Vienna), Medizinische Universität Wien = Medical University of Vienna, FAR, MCV, and MD acknowledge support from the French ANR (grant ANR‐13‐ISV8‐0002‐01), Institut Pasteur, CNRS, and the LABEX IBEID. FXH and KS acknowledge support from the Austrian Science Fund FWF., ANR-13-ISV8-0002,flavistem,La protéine E des flavivirus : interactions et fusion membranaire(2013), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)
Rok vydání: 2017
Předmět:
0301 basic medicine
flavivirus structure
viruses
Review
Biology
Antibodies
Viral
Biochemistry
Dengue fever
Flavivirus Infections
03 medical and health sciences
Epitopes
Structural Biology
antibody neutralization
Genetics
medicine
Animals
Humans
Antibody-dependent enhancement
antibody-dependent enhancement
Original antigenic sin
Molecular Biology
Antigens
Viral
[SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry
Molecular Biology/Structural Biology [q-bio.BM]
Viral Vaccine
Flavivirus
Viral Vaccines
fla- vivirus structure
medicine.disease
biology.organism_classification
Virology
Antibodies
Neutralizing
Microbiology
Virology & Host Pathogen Interaction
3. Good health
Vaccination
particle heterogeneity
030104 developmental biology
Immunization
Antibody Formation
antibody‐dependent enhancement
vaccine design
Synthetic Biology & Biotechnology
Zdroj: EMBO Reports
EMBO Reports, EMBO Press, 2018, 19 (2), pp.206-224. ⟨10.15252/embr.201745302⟩
EMBO Reports, 2018, 19 (2), pp.206-224. ⟨10.15252/embr.201745302⟩
ISSN: 1469-3178
1469-221X
Popis: International audience; Zika and dengue viruses belong to the Flavivirus genus, a close group of antigenically related viruses that cause significant arthro-pod-transmitted diseases throughout the globe. Although infection by a given flavivirus is thought to confer lifelong protection, some of the patient's antibodies cross-react with other flaviviruses without cross-neutralizing. The original antigenic sin phenomenon may amplify such antibodies upon subsequent heterologous flavivirus infection, potentially aggravating disease by antibody-dependent enhancement (ADE). The most striking example is provided by the four different dengue viruses, where infection by one serotype appears to predispose to more severe disease upon infection by a second one. A similar effect was postulated for sequential infections with Zika and dengue viruses. In this review, we analyze the molecular determinants of the dual antibody response to flavivirus infection or vaccination in humans. We highlight the role of conserved partially cryptic epitopes giving rise to cross-reacting and poorly neutralizing, ADE-prone antibodies. We end by proposing a strategy for developing an epitope-focused vaccine approach to avoid eliciting undesirable antibodies while focusing the immune system on producing protective antibodies only.
Databáze: OpenAIRE
Externí odkaz: