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Virus Res. 2014 Apr;183:67-74. doi: 10.1016/j.virusres.2014.01.027. Epub 2014 Feb 8.

Construction and characterization of a recombinant human adenovirus type 3 vector containing two foreign neutralizing epitopes in hexon.

Author information

1
State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou 510120 , China. Electronic address: 372546283@qq.com.
2
State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou 510120 , China. Electronic address: tianxingui7902@aliyun.com.
3
State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou 510120 , China. Electronic address: lixiao@gird.cn.
4
State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou 510120 , China. Electronic address: zzcmhxy003@163.com.
5
Department of Medical Genetics and Cell Biology, School of Basic Science, Guangzhou Medical University, Guangzhou 510120, China. Electronic address: xbsu92@yahoo.com.
6
State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Disease, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou 510120 , China. Electronic address: zhourong@gird.cn.

Abstract

The "antigen capsid-incorporation" strategy has been developed for adenovirus-based vaccines in the context of several diseases. Exogenous antigenic peptides incorporated into the adenovirus capsid structure can induce a robust and boosted antigen-specific immune response. Recently, we sought to generate a multivalent adenovirus type 3 (Ad3) vaccine vector by incorporating multiple epitopes into the major adenovirus capsid protein, hexon. In the present study, a multivalent recombinant Ad3 vaccine (R1R2A3) was constructed by homologous recombination, displaying two neutralizing epitopes from enterovirus type 71 (EV71) in hexon. The recombinant virus was confirmed by PCR, immunoblotting, and enzyme-linked immunosorbent assay, and injected into mice to analyze the epitope-specific humoral response. No differences were found between the viruses with two epitopes incorporated into the hypervariable regions (HVR1 and HVR2) of hexon and Ad3EGFP, based on thermostability and growth kinetic tests. Both the epitopes are thought to be exposed on the hexon-modified intact virion surface. The repeated administration of the modified adenovirus R1R2A3 to BALB/c mice boosted the humoral immune response against both epitopes. Immunization with recombinant virus R1R2A3 elicited higher IgG titers and higher neutralization titers against EV71 in vitro than immunization with the modified adenovirus with only one epitope incorporated into HVR1. In this study, the recombinant R1R2A3 virus expressing two exogenous neutralizing epitopes in hexon HVR1 and HVR2 induced specific immune responses to both foreign epitopes. Our study contributes to a better understanding of hexon-modified Ad vector as a multiple-epitope delivery vehicle.

KEYWORDS:

Ad vector; Epitope display; Hypervariable region; Immune response

PMID:
24518297
DOI:
10.1016/j.virusres.2014.01.027
[Indexed for MEDLINE]
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