Detection of post-vaccination enhanced dengue virus infection in macaques: An improved model for early assessment of dengue vaccines

Autor: Clarisse Lorin, Renato Sergio Marchevsky, Luiz Gustavo Almeida Mendes, Kirsten Schneider-Ohrum, Akira Homma, Maria Beatriz Borges, David W. Vaughn, Sébastien Baudart, Ouafaâ Tahmaoui, Marcos da Silva Freire, Yannick Vanloubbeeck, Renata Carvalho Pereira, Michael A. Cruz, Marie-Pierre Malice, Elena Caride, Leonardo Diniz-Mendes, Lucile Warter, Ygara S. Mendes
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Male
RNA viruses
Viral Diseases
Physiology
viruses
Dengue virus
Monkeys
medicine.disease_cause
Antibodies
Viral
Pathology and Laboratory Medicine
Dengue fever
Dengue Fever
Dengue
Immune Physiology
Medicine and Health Sciences
Public and Occupational Health
Biology (General)
Mammals
0303 health sciences
Vaccines
Innate Immune System
Immunogenicity
030302 biochemistry & molecular biology
Vaccination
Eukaryota
virus diseases
Vaccination and Immunization
Infectious Diseases
Medical Microbiology
Viral Pathogens
Vertebrates
Viruses
Cytokines
Female
Pathogens
Macaque
Research Article
Neglected Tropical Diseases
Primates
Infectious Disease Control
QH301-705.5
Immunology
Viremia
Dengue Vaccines
Microbiology
03 medical and health sciences
Virology
Old World monkeys
Genetics
medicine
Animals
Antibody-dependent enhancement
Molecular Biology
Microbial Pathogens
Dengue vaccine
030304 developmental biology
Biology and life sciences
Flaviviruses
business.industry
Organisms
Dengue Virus
Molecular Development
biochemical phenomena
metabolism
and nutrition
RC581-607
medicine.disease
Tropical Diseases
Antibodies
Neutralizing
Antibody-Dependent Enhancement
Macaca mulatta
Disease Models
Animal
Vaccines
Inactivated
Immune System
Inactivated vaccine
Amniotes
Parasitology
Preventive Medicine
Immunologic diseases. Allergy
business
Developmental Biology
Zdroj: PLoS Pathogens, Vol 15, Iss 4, p e1007721 (2019)
PLoS Pathogens
ISSN: 1553-7374
1553-7366
Popis: The need for improved dengue vaccines remains since the only licensed vaccine, Dengvaxia, shows variable efficacy depending on the infecting dengue virus (DENV) type, and increases the risk of hospitalization for severe dengue in children not exposed to DENV before vaccination. Here, we developed a tetravalent dengue purified and inactivated vaccine (DPIV) candidate and characterized, in rhesus macaques, its immunogenicity and efficacy to control DENV infection by analyzing, after challenge, both viral replication and changes in biological markers associated with dengue in humans. Although DPIV elicited cross-type and long-lasting DENV-neutralizing antibody responses, it failed to control DENV infection. Increased levels of viremia/RNAemia (correlating with serum capacity at enhancing DENV infection in vitro), AST, IL-10, IL-18 and IFN-γ, and decreased levels of IL-12 were detected in some vaccinated compared to non-vaccinated monkeys, indicating the vaccination may have triggered antibody-dependent enhancement of DENV infection. The dengue macaque model has been considered imperfect due to the lack of DENV-associated clinical signs. However, here we show that post-vaccination enhanced DENV infection can be detected in this model when integrating several parameters, including characterization of DENV-enhancing antibodies, viremia/RNAemia, and biomarkers relevant to dengue in humans. This improved dengue macaque model may be crucial for early assessment of efficacy and safety of future dengue vaccines.
Author summary Dengue virus (DENV) is responsible for the most widespread arboviral disease affecting humans. A pre-existing suboptimal immunity to DENV is accepted as being the major risk factor for severe dengue. Thus, if vaccination does not elicit optimal DENV-specific immunity, a vaccine might, instead, increase the risk of severe dengue in vaccinated individuals, as seen with the only licensed vaccine (Dengvaxia) in children naïve to DENV at vaccination. It is thus crucial to assess dengue vaccine safety at the earliest development stages, ideally in the preclinical stage. The dengue macaque model has been used to assess preclinical efficacy of dengue vaccines, with post-challenge DENV replication as the sole efficacy endpoint. However, this model had not predicted the Dengvaxia-associated safety signals. Here we characterized, in macaques, a dengue purified and inactivated vaccine (DPIV) candidate for its immunogenicity and efficacy/safety. Using a multiparameter approach, including characterization of viral replication and biomarkers relevant to dengue/severe dengue in humans, we were able to detect vaccine-associated safety signals in this model. While these results enabled us to discontinue at an early stage the DPIV development, this improved dengue macaque model may also be instrumental for early assessment of efficacy/safety of future dengue vaccines.
Databáze: OpenAIRE
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