Immunogenicity of an HIV virus-like particle vaccine

HIV病毒样颗粒疫苗的免疫原性

• 批准号: 6590286
• 负责人: FENG GAO
• 金额: $ 23.1万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-02-01 至 2005-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6590286
• 关键词: AIDS vaccines; HIV envelope protein gp120; Semliki Forest virus; biotechnology; cellular immunity; cytotoxic T lymphocyte; guinea pigs; helper T lymphocyte; human immunodeficiency virus 1; humoral immunity; immunomodulators; laboratory mouse; neutralizing antibody; recombinant proteins; recombinant virus; vaccine development; vaccinia virus; vector vaccine

Although AIDS has only been identified for 20 years, nearly 60 million people have been infected with human immunodeficiency viruses globally and currently 36 million of them are living with HIV infection. The most effective way to control the devastating disease is to develop a safe, practical, and effective vaccine that can either prevent new infection or slow down disease progression. Recent studies showed that both humoral and cellular immune responses are needed for such a vaccine. DNA prime and recombinant vaccinia virus boost exhibit a promising approach. We have developed a new DNA based dual semliki forest virus (SFV) expression system. The SFV vector expresses both codon-usage optimized gag and env genes in the form of virus-like particles (VLP) from the cells. Coupled with high expression nature of SFV vector and optimized HIV-1 genes, we expect high expression level of viral proteins in natural viral conformation will elicit both neutralizing antibody and CTL responses in animals. Now we are proposing to evaluate the newly developed unique DNA vaccine candidate in guinea pigs and mice for HIV specific humoral and cellular immune responses. The animals will be immunized with DNA alone for production of VLP in vivo and then boosted with either autologous rgpl20 or recombinant vaccinia viruses expressing autologous gag or env genes. We will collect serum samples from guinea pigs to determine if higher titers of neutralizing antibody will be elicited by the SFV vector that express both gag and env genes, and if humoral immune response can be further augmented by either rgpl20 or recombinant vaccinia virus that expresses env gene. We will also isolate the splenocytes from immunized mice to determine if VLPs generated by our newly developed dual expression SFV vector can induce strong CTL response alone or with recombinant vaccinia virus boost, if both CD4 and CD8 responses will be induced by VLPs, and if VLPs can induce better and broader CTL responses than either the gag or env gene alone. Results from this study will determine if VLPs generated by dual expression SFV vector in vivo can bc developed into an effective AIDS vaccine and used as a guideline to design better immunization strategies in mice and guinea pigs or higher level animals, like monkeys.

尽管艾滋病仅被发现了20年，但在全球范围内已有近6000万人感染了人类免疫缺陷病毒，目前有3600万人患有艾滋病毒感染。控制毁灭性疾病的最有效方法是开发一种安全，实用和有效的疫苗，该疫苗可以防止新的感染或减缓疾病进展。最近的研究表明，这种疫苗都需要体液和细胞免疫反应。 DNA Prime和重组疫苗病毒的增强表现出一种有希望的方法。我们已经开发了一种新的基于DNA的双重Semliki森林病毒（SFV）表达系统。 SFV矢量在该中表达密码子使用优化的GAG和ENV基因 来自细胞的病毒样颗粒（VLP）的形式。再加上SFV载体的高表达性质和优化的HIV-1基因，我们期望天然病毒构象中病毒蛋白的高表达水平将引起动物中和中和抗体和CTL反应。现在，我们提议评估豚鼠和小鼠中新开发的独特的DNA疫苗候选者，以用于HIV特异性的体液和细胞免疫反应。这些动物将仅用DNA免疫以生产体内VLP，然后用自体RGPL20或表达自体GAG或ENV基因的重组疫苗病毒提升。我们将从豚鼠中收集血清样品，以确定表达GAG和ENV基因的SFV载体是否会引起中和抗体的较高滴度，以及是否可以进行体液免疫反应 通过RGPL20或表达ENV基因的重组离子病毒进一步增强。 We will also isolate the splenocytes from immunized mice to determine if VLPs generated by our newly developed dual expression SFV vector can induce strong CTL response alone or with recombinant vaccinia virus boost, if both CD4 and CD8 responses will be induced by VLPs, and if VLPs can induce better and broader CTL responses than either the gag or env gene alone.这项研究的结果将确定体内双表达SFV载体产生的VLP是否可以BC发展为有效的AIDS疫苗，并用作在小鼠和豚鼠或更高水平的动物（如猴子）中设计更好的免疫策略的指南。