Vaccines Based on Novel Adeno-Associated Virus Vectors Elicit Aberrant CD8 + T-Cell Responses in Mice

Author:

Lin Jianping1,Zhi Yan1,Mays Lauren1,Wilson James M.1

Affiliation:

1. Gene Therapy Program, Department of Pathology and Laboratory Medicine, University of Pennsylvania, 125 S. 31st Street, Philadelphia, Pennsylvania 19104

Abstract

ABSTRACT We recently discovered an expanded family of adeno-associated viruses (AAVs) that show promise as improved gene therapy vectors. In this study we evaluated the potential of vectors based on several of these novel AAVs as vaccine carriers for human immunodeficiency virus type 1 Gag. Studies with mice indicated that vectors based on AAV type 7 (AAV7), AAV8, and AAV9 demonstrate improved immunogenicity in terms of Gag CD8 + T-cell and Gag antibody responses. The quality of these antigen-specific responses was evaluated in detail for AAV2/8 vectors and compared to results with an adenovirus vector expressing Gag (AdC7). AAV2/8 produced a vibrant CD8 + T-cell effector response characterized by coexpression of gamma interferon and tumor necrosis factor alpha as well as in vivo cytolytic activity. No CD8 + T-cell response generated by any of the AAVs was effectively boosted with AdC7, a result consistent with the finding of a relative lack of cells expressing interleukin-2 (IL-2) or a central memory phenotype at 3 months after the prime. The primary response to an AdC7 vaccine differed from that generated by AAVs in that the peak effector response evolved into populations of Gag-specific T cells expressing high levels of cytokines, including IL-2, and with effector memory and central memory phenotypes. A number of mechanisms could be considered to explain the aberrant activation of CD8 + T cells by AAV, including insufficient inflammatory responses, CD4 help, and/or chronic antigen expression and T-cell exhaustion. Interestingly, the B-cell response to AAV-encoded Gag was quite vibrant and easily boosted with AdC7.

Publisher

American Society for Microbiology

Subject

Virology,Insect Science,Immunology,Microbiology

Cited by 56 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3