Tests in mice of a dengue vaccine candidate made of chimeric Junin virus-like particles and conserved dengue virus envelope sequences

Autor: Cristina Silvia Borio, Mario Enrique Lozano, Vania Aparecida Mareze, Santiago Mirazo, Renata C. Fleith, Marcos Fabian Bilen, Juan Arbiza, Daniel S. Mansur, Oscar Bruna-Romero
Rok vydání: 2015
Předmět:
0301 basic medicine
CIENCIAS MÉDICAS Y DE LA SALUD
junin
viruses
Dengue Vaccines
Viral Plaque Assay
vlps
Tecnologías que involucran la identificación de ADN
proteínas y enzimas
y cómo influyen en el conjunto de enfermedades y mantenimiento del bienestar
Dengue virus
Antibodies
Viral
medicine.disease_cause
Applied Microbiology and Biotechnology
Neutralization
Biotecnología de la Salud
Dengue fever
law.invention
03 medical and health sciences
Viral Envelope Proteins
Neutralization Tests
law
vaccine
medicine
Animals
Vaccines
Virus-Like Particle
Neutralizing antibody
Dengue vaccine
Drug Carriers
Vaccines
Synthetic
Junin virus
biology
virus diseases
General Medicine
Dengue Virus
biochemical phenomena
metabolism
and nutrition
medicine.disease
biology.organism_classification
Antibodies
Neutralizing
dengue
Virology
Mice
Inbred C57BL
Treatment Outcome
030104 developmental biology
biology.protein
Recombinant DNA
Antibody
Biotechnology
Zdroj: Applied Microbiology and Biotechnology. 100:125-133
ISSN: 1432-0614
0175-7598
Popis: Two new vaccine candidates against dengue virus (DENV) infection were generated by fusing the coding sequences of the self-budding Z protein from Junin virus (Z-JUNV) to those of two cryptic peptides (Z/DENV-P1 and Z/DENV-P2) conserved on the envelope protein of all serotypes of DENV. The capacity of these chimeras to generate virus-like particles (VLPs) and to induce virus-neutralizing antibodies in mice was determined. First, recombinant proteins that displayed reactivity with a Z-JUNV-specific serum by immunofluorescence were detected in HEK-293 cells transfected with each of the two plasmids and VLP formation was also observed by transmission electron microscopy. Next, we determined the presence of antibodies against the envelope peptides of DENV in the sera of immunized C57BL/6 mice. Results showed that those animals that received Z/DENV-P2 DNA coding sequences followed by a boost with DENV-P2 synthetic peptides elicited significant specific antibody titers (≥6.400). Finally, DENV plaque-reduction neutralization tests (PRNT) were performed. Although no significant protective effect was observed when using sera of Z/DENV-P1-immunized animals, antibodies raised against vaccine candidate Z/DENV-P2 (diluted 1:320) were able to reduce in over 50 % the number of viral plaques generated by infectious DENV particles. This reduction was comparable to that of the 4G2 DENV-specific monoclonal cross-reactive (all serotypes) neutralizing antibody. We conclude that Z-JUNV-VLP is a valid carrier to induce antibody-mediated immune responses in mice and that Z/DENV-P2 is not only immunogenic but also protective in vitro against infection of cells with DENV, deserving further studies. On the other side, DENV´s fusion peptide-derived chimera Z/DENV-P1 did not display similar protective properties Fil: Mareze, Vania Aparecida. 1UNIVERSIDADE FEDERAL DE SANTA CATARINA; Fil: Cristina, Borio. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnologia; Argentina Fil: Bilen, Marcos Fabian. Universidad Nacional de Quilmes. Departamento de Ciencia y Tecnologia; Argentina Fil: Fleith, Renata. Universidade Federal Da Santa Catarina; Brasil Fil: Mirazo, Santiago. Universidad de la Republica; Uruguay Fil: Santos Mansur, Daniel. Universidade Federal Da Santa Catarina; Brasil Fil: Bruña Romero, Oscar. Universidade Federal Da Santa Catarina; Brasil Fil: Arbiza, Juan. Universidad de la Republica; Uruguay Fil: Mario Enrique, Lozano. Universidad Nacional de Quilmes; Argentina
Databáze: OpenAIRE
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