Targeting the Non-structural Protein 1 from Dengue Virus to a Dendritic Cell Population Confers Protective Immunity to Lethal Virus Challenge

Autor(es):Mostrar menos -

Henriques, Hugo R. ^[1] ; Rampazo, Eline V. ^[1] ; Goncalves, Antonio J. S. ^[2] ; Vicentin, Elaine C. M. ^[1] ; Amorim, Jaime H. ^[3] ; Panatieri, Raquel H. ^[1] ; Amorim, Kelly N. S. ^[1] ; Yamamoto, Marcio M. ^[1] ; Ferreira, Luis C. S. ^{[3, 4]} ; Alves, Ada M. B. ^{[2, 4]} ; Boscardin, Silvia B. ^{[1, 4]}

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Lab Antigen Targeting Dendrit Cells, Dept Parasitol, Sao Paulo - Brazil

^[2] Fundacao Oswaldo Cruz, Lab Biotechnol & Physiol Viral Infect, Inst Oswaldo Cruz, Rio De Janeiro - Brazil

^[3] Univ Sao Paulo, Lab Vaccine Dev, Dept Microbiol, Sao Paulo - Brazil

^[4] Natl Inst Sci & Technol Vaccines, Belo Horizonte, MG - Brazil

• Tipo de documento: Artigo Científico
• Fonte: PLoS Neglected Tropical Diseases; v. 7, n. 7 JUL 2013.
• Citações Web of Science: 30

Resumo

Dengue is the most prevalent arboviral infection, affecting millions of people every year. Attempts to control such infection are being made, and the development of a vaccine is a World Health Organization priority. Among the proteins being tested as vaccine candidates in preclinical settings is the non-structural protein 1 (NS1). In the present study, we tested the immune responses generated by targeting the NS1 protein to two different dendritic cell populations. Dendritic cells (DCs) are important antigen presenting cells, and targeting proteins to maturing DCs has proved to be an efficient means of immunization. Antigen targeting is accomplished by the use of a monoclonal antibody (mAb) directed against a DC cell surface receptor fused to the protein of interest. We used two mAbs (alpha DEC205 and alpha DCIR2) to target two distinct DC populations, expressing either DEC205 or DCIR2 endocytic receptors, respectively, in mice. The fusion mAbs were successfully produced, bound to their respective receptors, and were used to immunize BALB/c mice in the presence of polyriboinosinic: polyribocytidylic acid (poly (I:C)), as a DC maturation stimulus. We observed induction of strong anti-NS1 antibody responses and similar antigen binding affinity irrespectively of the DC population targeted. Nevertheless, the IgG1/IgG2a ratios were different between mouse groups immunized with alpha DEC-NS1 and alpha DCIR2-NS1 mAbs. When we tested the induction of cellular immune responses, the number of IFN-gamma producing cells was higher in alpha DEC-NS1 immunized animals. In addition, mice immunized with the alpha DEC-NS1 mAb were significantly protected from a lethal intracranial challenge with the DENV2 NGC strain when compared to mice immunized with alpha DCIR2-NS1 mAb. Protection was partially mediated by CD4(+) and CD8(+) T cells as depletion of these populations reduced both survival and morbidity signs. We conclude that targeting the NS1 protein to the DEC205(+) DC population with poly (I:C) opens perspectives for dengue vaccine development. (AU)

• Processo FAPESP: 10/03079-9 - Análise das respostas adaptativas quando um antígeno do vírus da dengue é direcionado para duas populações distintas de células dendríticas.
• Beneficiário: Hugo Rezende Henriques
• Modalidade de apoio: Bolsas no Brasil - Mestrado
• Processo FAPESP: 11/51761-6 - Estrategias vacinais voltadas para o controle da dengue baseadas em proteinas recombinantes e adjuvantes de natureza microbiana.
• Beneficiário: Luis Carlos de Souza Ferreira
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 07/08648-9 - Direcionamento de antígenos recombinantes para células dendríticas in vivo: uma nova estratégia para o desenvolvimento de vacinas
• Beneficiário: Silvia Beatriz Boscardin
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores