The successful induction of T-cell and antibody responses by a recombinant measles virus-vectored tetravalent dengue vaccine provides partial protection against dengue-2 infection

Hum Vaccin Immunother. 2016 Jul 2;12(7):1678-89. doi: 10.1080/21645515.2016.1143576. Epub 2016 Feb 22.

Abstract

Dengue has a major impact on global public health, and the use of dengue vaccine is very limited. In this study, we evaluated the immunogenicity and protective efficacy of a dengue vaccine made from a recombinant measles virus (MV) that expresses envelope protein domain III (ED3) of dengue-1 to 4. Following immunization with the MV-vectored dengue vaccine, mice developed specific interferon-gamma and antibody responses against dengue virus and MV. Neutralizing antibodies against MV and dengue viruses were also induced, and protective levels of FRNT50 ≥ 10 to 4 serotypes of dengue viruses were detected in the MV-vectored dengue vaccine-immunized mice. In addition, specific interferon-gamma and antibody responses to dengue viruses were still induced by the MV-vectored dengue vaccine in mice that were pre-infected with MV. This finding suggests that the pre-existing immunity to MV did not block the initiation of immune responses. By contrast, mice that were pre-infected with dengue-3 exhibited no effect in terms of their antibody responses to MV and dengue viruses, but a dominant dengue-3-specific T-cell response was observed. After injection with dengue-2, a detectable but significantly lower viremia and a higher titer of anti-dengue-2 neutralizing antibodies were observed in MV-vectored dengue vaccine-immunized mice versus the vector control, suggesting that an anamnestic antibody response that provided partial protection against dengue-2 was elicited. Our results with regard to T-cell responses and the effect of pre-immunity to MV or dengue viruses provide clues for the future applications of an MV-vectored dengue vaccine.

MeSH terms

  • Animals
  • Antibodies, Neutralizing / blood
  • Antibodies, Viral / blood
  • Antibody Formation*
  • Dengue Vaccines / administration & dosage
  • Dengue Vaccines / genetics
  • Dengue Vaccines / immunology*
  • Drug Carriers*
  • Interferon-gamma / metabolism
  • Measles virus / genetics*
  • Measles virus / immunology
  • Mice, Inbred C57BL
  • T-Lymphocytes / immunology*
  • Vaccines, Synthetic / administration & dosage
  • Vaccines, Synthetic / genetics
  • Vaccines, Synthetic / immunology

Substances

  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Dengue Vaccines
  • Drug Carriers
  • Vaccines, Synthetic
  • Interferon-gamma