Immunogenicity and efficacy of chimeric dengue vaccine (DENVax) formulations in interferon-deficient AG129 mice

Details

• Alternative Title:
  Vaccine
• Personal Author:
  Brewoo, Joseph N. ; Kinney, Richard M. ; Powell, Tim D. ; Arguello, John J. ; Silengo, Shawn J. ; Partidos, Charalambos D. ; Huang, Claire Y.-H. ; Stinchcomb, Dan T. ; Osorio, Jorge E.
• Description:
  Formulations of chimeric dengue vaccine (DENVax) viruses containing the pre-membrane (prM) and envelope (E) genes of serotypes 1-4 expressed in the context of the attenuated DENV-2 PDK-53 genome were tested for safety, immunogenicity and efficacy in interferon receptor knock-out mice (AG129). Monovalent formulations were safe and elicited robust neutralizing antibody responses to the homologous virus and only limited cross-reactivity to other serotypes. A single dose of monovalent DENVax-1, -2, or -3 vaccine provided eighty or greater percent protection against both wild-type (wt) DENV-1 (Mochizuki strain) and DENV-2 (New Guinea C strain) challenge viruses. A single dose of monovalent DENVax-4 also provided complete protection against wt DENV-1 challenge and significantly increased the survival times after challenge with wt DENV-2. In studies using tetravalent mixtures, DENVax ratios were identified that: (i) caused limited viremia, (ii) induced serotype-specific neutralizing antibodies to all four DENV serotypes with different hierarchies, and (iii) conferred full protection against clinical signs of disease following challenge with either wt DENV-1 or DENV-2 viruses. Overall, these data highlight the immunogenic profile of DENVax, a novel candidate tetravalent dengue vaccine and the advantage of sharing a common attenuated genomic backbone among the DENVax monovalent vaccines that confer protection against homologous or heterologous virus challenge.
• Subjects:
  Animals Antibodies, Neutralizing Antibodies, Viral Body Temperature Body Weight Dengue Dengue Vaccines Disease Models, Animal Interferons Mice Mice, Knockout Survival Analysis Vaccines, Attenuated Vaccines, Synthetic Viral Load Viremia

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• Keywords:
  AG129 Mice Dengue 2 PDK-53 Chimeras Dengue Vaccines DENVax
• Source:
  Vaccine. 30(8):1513-1520
• Pubmed ID:
  22178727
• Pubmed Central ID:
  PMC4592107
• Document Type:
  Journal Article
• Funding:
  U01 AI070443-04/AI/NIAID NIH HHSUnited States/ ; U01 AI070443-01/AI/NIAID NIH HHSUnited States/ ; 5-U01-AI070443/AI/NIAID NIH HHSUnited States/ ; CC999999/ImCDC/Intramural CDC HHSUnited States/ ; U01 AI070443/AI/NIAID NIH HHSUnited States/ ; U01 AI070443-03/AI/NIAID NIH HHSUnited States/ ; U01 AI070443-02/AI/NIAID NIH HHSUnited States/
• Volume:
  30
• Issue:
  8
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha-512:ad0ac7c9e7af13e663c4a2ce6d93384efec6ded578f737243eeacd1acffd93e31ae00462fbb88b90c680d87881b044246b10a1576362cb0796b793a2843b411d
• Download URL:
  https://stacks.cdc.gov/view/cdc/34674/cdc_34674_DS1.pdf
• File Type:
  [PDF - 734.56 KB ]