Chimeric dengue type 2 (vaccine strain PDK-53)/dengue type 1 virus as a potential candidate dengue type 1 virus vaccine
Autor(es): Huang, CYH; Butrapet, S; Pierro, DJ; Chang, GJJ; Hunt, AR; Bhamarapravati, N; Gubler, DJ; Kinney, RM
Resumo: 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-I 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-MK2 cells, less efficient replication in C6/36 cells, and attenuation for mice. These chimeric viruses elicited higher mouse neutralizing antibody titers against DEN-I virus than did the candidate DEN-I 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-I 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.
Palavras-Chave: Yellow fever virus; Tick borne encephalitis; Aedes aegypti; Hemorrhagic fever; Oral infection; Shock syndrome; Risk factors; Construction; Volunteers; Protein
Imprenta: Journal of Virology, v. 74, n. 7, p. 3020-3028, 2000
Identificador do objeto digital: 10.1128/JVI.74.7.3020-3028.2000
Descritores: Aedes aegypti - Cell ; Aedes aegypti - Genome ; Aedes aegypti - Virus
Data de publicação: 2000
