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Chimeric dengue type 2/type 1 viruses induce immune responses in cynomolgus monkeys.

Siritorn Butrapet1, Jundee Rabablert, Subhkij Angsubhakorn

  • 1Center for Vaccine Development, Institute of Science and Technology for Research and Development, Mahidol University, Bangkok, Thailand.

The Southeast Asian Journal of Tropical Medicine and Public Health
|April 16, 2003
PubMed
Summary
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Chimeric dengue virus vaccines (DEN2/1) successfully induced neutralizing antibodies in monkeys without causing viremia. These safe and broadly immunogenic DEN2/1 viruses show promise as live-attenuated vaccine candidates.

Area of Science:

  • Virology
  • Immunology
  • Vaccinology

Background:

  • Dengue virus poses a significant global health threat.
  • Development of safe and effective dengue vaccines is a priority.

Purpose of the Study:

  • To evaluate the immunogenicity and safety of chimeric dengue type 2/type 1 (DEN2/1) viruses in cynomolgus monkeys.
  • To assess the protective efficacy of DEN2/1 viruses against wild-type dengue virus challenge.

Main Methods:

  • Construction of DEN2/1 chimeric viruses with DEN-1 structural genes and DEN-2 nonstructural genes.
  • Immunization of cynomolgus monkeys with DEN2/1 viruses.
  • Assessment of neutralizing antibody responses, viremia, and immune markers (interferon gamma, soluble interleukin 2 receptor) after immunization and challenge with wild-type dengue viruses (DEN1 and DEN2).

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Main Results:

  • DEN2/1 viruses induced DEN1 virus-specific neutralizing antibodies and IgM in monkeys without viremia.
  • Chimeric virus immunization reduced viremia upon challenge with wild-type DEN1 virus.
  • No significant increase in T-cell activation markers suggests reduced immunopathogenesis.
  • No correlation found between neutralizing antibody levels and viremia incidence.

Conclusions:

  • DEN2/1 chimeric viruses demonstrate safety, broad immunogenicity, and reduced immunopathogenicity in a primate model.
  • These findings support the potential of DEN2/1 viruses as live-attenuated dengue vaccine candidates.