Protective Immunity

保护性免疫

• 批准号: 8307106
• 负责人: David I Watkins
• 金额: $ 51.45万
• 依托单位: UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-07-01 至 2017-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8307106
• 关键词: AIDS vaccine development; Acute; Adenoviruses; Animals; Chronic Phase; Cytomegalovirus; Electroporation; Flavivirus; Gagging; Genes; HIV; HIV vaccine; Human; Immune response; Immunity; Institutes; Instruction; Intention; Interleukin-12; Life; Macaca; Macaca mulatta; Monkeys; Open Reading Frames; Outcome; Plasmids; Proteins; Proteome; Recombinant DNA; Recombinants; SIV; Serotyping; T cell response; Testing; Vaccinated; Vaccination; Vaccine Design; Vaccines; Viral; Virus; Yellow Fever; Yellow Fever Vaccine; design; improved; nonhuman primate; novel vaccines; prevent; research study; vector

We hypothesize that a recombinant yellow fever vaccine (rYF) or rDNA (delivered by electroporation along with IL-12; EP+IL-12) prime followed by a recombinant adenovirus serotype 35 (rAd35) boost can control viral replication after either a homologous or heterologous AIDS virus challenge. We plan to test this hypothesis in macaques using rigorous challenges with the highly pathogenic SIV isolates, SIVmac251 and SIVsmE660. In a previous study, we found that a rDNA prime followed by a rAd5 boost (encoding all of the SIVmac239 proteins except for Env) reduced acute and chronic phase replication after a pathogenic SIVsmE660 mucosal challenge in six of eight vaccinated Indian rhesus macaques. Indeed, six of the vaccinees have no detectable viral replication at one year post challenge. This positive outcome is exceedingly rare in vaccine experiments using a pathogenic SIV challenge. We also discovered that vaccineinduced T cell responses against Gag and Vif correlated with this good outcome. We postulate that there are additional targets in the SIV proteome that can induce efficacious T cell responses. More recently our colleagues at lAVI have shown that vaccination with rDNA plasmids encoding all of the SIV proteins (including Env) by EP along with a plasmid encoding IL-12, followed by a rAd5 boost reduced viral replication of the highly pathogenic SIVmac239 challenge virus in seven of eight macaques. Indeed these vaccine results, along with the recent findings of Louis Picker using recombinant rhesus cytomegalovirus (rhCMV) vectors are the most encouraging non-human primate vaccine results to date. Our intention now is to perform a vaccine study to determine which of the SIV proteins are important targets for the control of viral replication in our first specific aim. In an attempt to improve upon these last two experiments we will also include newly discovered cryptic open reading frames (cORFs) in the vaccine. Our second specific aim is to determine whether a rYF or rDNA (EP+IL-12) prime followed by a rAd35 boost can control viral replication after either a homologous or heterologous AIDS virus challenge.

我们假设重组黄热病疫苗（rYF）或rDNA（通过电穿孔递送）可以在免疫系统中进行