A rapid strategy for constructing novel simian adenovirus vectors with high viral titer and expressing highly antigenic proteins applicable for vaccine development.
Virus Res
; 268: 1-10, 2019 07 15.
Article
em En
| MEDLINE
| ID: mdl-31108113
ABSTRACT
Adenoviral vectors have been widely used for the development of infectious disease vaccines. However, the challenge of human adenoviral vector rooted from the predominant adenovirus serotype 5 strain limiting its usefulness by the widespread pre-existing neutralizing antibodies in recipients. To circumvent this obstacle, we generated an ad-hoc adenovirus vector in human or primates. Here, a chimeric simian adenoviral vector Sad23 was constructed consisting in deleting of E1 and E3 regions of the full-length simian adenovirus serotype 23 genome (SAdV23) by Gibson assembly. To improve Sad23 virus propagating efficiency, the E4 region open reading frame 6 (orf6) was replaced by the corresponding element of human adenovirus type 5 (Ad5), designated Sad23L. The procedure for cloning this novel vector took a single week, and recombinant adenovirus was packaged with high titer in HEK293 cells. To verify the ability of this novel adenoviral vector to deliver foreign genes, Zika virus (ZIKV) prM-E genes were used as target genes for antigen expression. Recombinant adenoviruses Sad23L-prM-E, Sad23-prM-E and Ad5-prM-E were intramuscularly inoculated into Ad5-eGFP none pre-exposed or pre-exposed mice, and the immune response to ZIKV prM-E was compared between vectors. Sad23L-prM-E induced a fairly robust immune response and maintained immunogenicity in Ad5 pre-exposed mice, which suggested that Ad5 pre-existing immunity did not affect Sad23L-prM-E immunization. These preliminary results suggest that the proposed rapid strategy was effective in constructing a new adenoviral vector platform (Sad23 L) usable for the development of human vaccines.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Contexto em Saúde:
1_ASSA2030
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2_ODS3
Base de dados:
MEDLINE
Assunto principal:
Vacinas Virais
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Adenovirus dos Símios
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Carga Viral
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Vetores Genéticos
Limite:
Animals
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Female
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Humans
Idioma:
En
Revista:
Virus Res
Ano de publicação:
2019
Tipo de documento:
Article