Intranasal vaccination with a helper-dependent adenoviral vector enhances transgene-specific immune responses in BALB/c mice.
Helper-dependent adenoviral (HDAd) vectors were developed primarily for genetic disease therapy by deleting all coding regions for attenuating the host cellular immune response to adenovirus (Ad) and long-lasting gene expression. Recently Harui et al. reported that HDAd vaccine could stimulate superior transgene-specific cytotoxic T lymphocyte (CTL) and antibody responses via the intraperitoneal route, compared to first-generation adenoviral (FGAd) vaccine. This prompted us to explore the potential of HDAd as a vaccine vector administrated intranasally. In this study, we prepared HDAd and FGAd vectors expressing enhanced green fluorescent protein (EGFP), respectively, and compared their efficacy in mice. Mice were immunized intranasally with 5x10(9) vp HDAd or FGAd vector particles. Despite stimulating similar anti-Ad antibody responses with FGAd vaccine in the prime/boost strategy, HDAd vector expressing EGFP displayed superior transgene-specific serum IgG, mucosal IgA and cellular immune response, with the characterization of balanced or mixed Th1/Th2 CD4+ T-cell responses. Meanwhile, a single dose of intranasal (i.n.) vaccine of HDAd-EGFP induced a serum IgG response with more efficacy than FGAd-EGFP. In addition, i.n. boost immunization enhanced transgene-specific humoral and cellular responses, compared to single i.n. HDAd-EGFP immunization. Our results suggest that HDAd has potential for a mucosal vaccine vector via i.n. route, which will be useful for the development of vaccines against respiratory viruses, such as respiratory syncytial virus and influenza virus.
Fu
Yuan-hui
YH
College of Life Sciences & Bioengineering, Beijing Jiaotong University, Beijing 100044, China.
He
Jin-sheng
JS
Zheng
Xian-xian
XX
Wang
Xiao-bo
XB
Xie
Can
C
Shi
Chang-xin
CX
Zhang
Mei
M
Tang
Qian
Q
Wei
Wei
W
Qu
Jian-guo
JG
Hong
Tao
T
D000256:Adenoviridae / Q000276:immunology*; D000257:Adenoviridae Infections / Q000517:prevention & control; D000281:Administration, Intranasal; D000818:Animals; D005822:Genetic Vectors / Q000008:administration & dosage / Q000276:immunology*; D049452:Green Fluorescent Proteins / Q000276:immunology; D006378:Helper Viruses / Q000276:immunology*; D007074:Immunoglobulin G / Q000097:blood; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D019076:Transgenes; D014611:Vaccination; D014765:Viral Vaccines / Q000008:administration & dosage / Q000276:immunology*
D007074:Immunoglobulin G; D014765:Viral Vaccines; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins