Chimeric dengue type 2 (vaccine strain PDK-53)/dengue type 1 virus as a potential candidate dengue type 1 virus vaccine.
We constructed chimeric dengue type 2/type 1 (DEN-2/DEN-1) viruses containing the nonstructural genes of DEN-2 16681 virus or its vaccine derivative, strain PDK-53, and the structural genes (encoding capsid protein, premembrane protein, and envelope glycoprotein) of DEN-1 16007 virus or its vaccine derivative, strain PDK-13. We previously reported that attenuation markers of DEN-2 PDK-53 virus were encoded by genetic loci located outside the structural gene region of the PDK-53 virus genome. Chimeric viruses containing the nonstructural genes of DEN-2 PDK-53 virus and the structural genes of the parental DEN-1 16007 virus retained the attenuation markers of small plaque size and temperature sensitivity in LLC-MK(2) cells, less efficient replication in C6/36 cells, and attenuation for mice. These chimeric viruses elicited higher mouse neutralizing antibody titers against DEN-1 virus than did the candidate DEN-1 PDK-13 vaccine virus or chimeric DEN-2/DEN-1 viruses containing the structural genes of the PDK-13 virus. Mutations in the envelope protein of DEN-1 PDK-13 virus affected in vitro phenotype and immunogenicity in mice. The current PDK-13 vaccine is the least efficient of the four Mahidol candidate DEN virus vaccines in human trials. The chimeric DEN-2/DEN-1 virus might be a potential DEN-1 virus vaccine candidate. This study indicated that the infectious clones derived from the candidate DEN-2 PDK-53 vaccine are promising attenuated vectors for development of chimeric flavivirus vaccines.
Huang
C Y
CY
Division of Vector-Borne Infectious Diseases, Centers for Disease Control and Prevention, U.S. Department of Health and Human Services, Fort Collins, Colorado 80522, USA.
Butrapet
S
S
Pierro
D J
DJ
Chang
G J
GJ
Hunt
A R
AR
Bhamarapravati
N
N
Gubler
D J
DJ
Kinney
R M
RM
D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D002678:Chimera; D017931:DNA Primers; D003716:Dengue Virus / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity; D016679:Genome, Viral; D051379:Mice; D008813:Mice, Inbred ICR; D009420:Nervous System / Q000821:virology; D014765:Viral Vaccines / Q000235:genetics / Q000276:immunology*; D014774:Virulence
D017931:DNA Primers; D014765:Viral Vaccines