Targeting the non-structural protein 1 from dengue virus to a dendritic cell population confers protective immunity to lethal virus challenge

PLoS Negl Trop Dis. 2013 Jul 18;7(7):e2330. doi: 10.1371/journal.pntd.0002330. Print 2013.


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 (αDEC205 and αDCIR2) 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 αDEC-NS1 and αDCIR2-NS1 mAbs. When we tested the induction of cellular immune responses, the number of IFN-γ producing cells was higher in αDEC-NS1 immunized animals. In addition, mice immunized with the αDEC-NS1 mAb were significantly protected from a lethal intracranial challenge with the DENV2 NGC strain when compared to mice immunized with αDCIR2-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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / administration & dosage
  • Animals
  • Antibodies, Monoclonal / administration & dosage
  • Antibodies, Viral / blood
  • CD4-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / immunology
  • Dendritic Cells / immunology*
  • Dengue / prevention & control*
  • Dengue Vaccines / administration & dosage
  • Dengue Vaccines / immunology*
  • Dengue Virus / immunology*
  • Disease Models, Animal
  • Humans
  • Immunoglobulin G / blood
  • Interferon-gamma / metabolism
  • Leukocytes, Mononuclear / immunology
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Poly I-C / administration & dosage
  • Protein Transport
  • Survival Analysis
  • Viral Nonstructural Proteins / immunology*


  • Adjuvants, Immunologic
  • Antibodies, Monoclonal
  • Antibodies, Viral
  • Dengue Vaccines
  • Immunoglobulin G
  • NS1 protein, Flavivirus
  • Viral Nonstructural Proteins
  • Interferon-gamma
  • Poly I-C

Grant support

This research was supported by the Brazilian National Research Council (CNPq)/National Institutes of Science and Technology in Vaccines (INCTV, 15203*12), São Paulo State Research Funding Agency (FAPESP, 2007/08648-9, 2011/51761-6), BNP-Paribas Bank and Rio de Janeiro State Research Funding Agency (FAPERJ). HRH and JHA received fellowships from FAPESP (2010/03079-9 and 2009/5033-7) and EVR received a fellowship from CAPES. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.