HIV/FIV-cat model: a model to identify vaccine epitopes

HIV/FIV-cat 模型：识别疫苗表位的模型

• 批准号: 7469353
• 负责人: Janet K. Yamamoto
• 金额: $ 35.08万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-07-01 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7469353
• 关键词: Adjuvant; Animals; Antibodies; Antigens; Cellular Immunity; Common Epitope; Cytotoxic T-Lymphocytes; Development; Epitopes; Feline Immunodeficiency Virus; Feline immunodeficiency virus p24 protein; Felis catus; Future; HIV Seropositivity; HIV-1; HIV-1 vaccine; Human; Immunity; Individual; Infection; Laboratories; Mediating; Modeling; Molecular; Peptides; Peripheral Blood Mononuclear Cell; Proteins; Rate; Recombinant Proteins; Reporting; SIV; Sequence Analysis; Specific Pathogen Frees; Vaccinated; Vaccines; Virus; base; germ free condition; immunogenic; immunogenicity; innovation; prevent; vaccine development; Adjuvant; Animals; Antibodies; Antigens; Cellular Immunity; Common Epitope; Cytotoxic T-Lymphocytes; Development; Epitopes; Feline Immunodeficiency Virus; Feline immunodeficiency virus p24 protein; Felis catus; Future; HIV Seropositivity; HIV-1; HIV-1 vaccine; Human; Immunity; Individual; Infection; Laboratories; Mediating; Modeling; Molecular; Peptides; Peripheral Blood Mononuclear Cell; Proteins; Rate; Recombinant Proteins; Reporting; SIV; Sequence Analysis; Specific Pathogen Frees; Vaccinated; Vaccines; Virus; base; germ free condition; immunogenic; immunogenicity; innovation; prevent; vaccine development

DESCRIPTION (provided by applicant): Recent discovery in our laboratory revealed that 77-78% of specific-pathogen-free (SPF) cats immunized with clade B HIV-1/UCD1 vaccine were protected against subsequent FIV infection. Based on sequence analysis of HIV-1/UCD1 and FIV p24 proteins, a significant protection rate was achieved against FIV infection with a vaccine consisting of only HIV-1 p24 protein whose sequence was so distinctly different from the challenge virus. HIV-1 p24 vaccines were more effective than FIV p24 vaccines derived from pathogenic FIV strains. In fact, enhancement of FIV challenge infection was observed in the FIV p24-vaccinated cats. These findings suggest that selection of HIV-1 immunogen is essential to the development of an effective HIV-1 vaccine. Two specific aims are proposed to identify cross-protective HIV-1 p24 epitopes that may be useful as HIV-1 vaccine immunogens for humans. Specific Aim 1 will identify the cross-protective epitope(s) on HIV-1 clade B p24 using HIV/FIV-cat model and characterize the immunity induced by the protective epitopes. Specific Aim 2 will determine the relevance of the conserved protective epitopes identified in the HIV/FIV-cat model to HIV-1 vaccine development of humans. Studies will be performed to determine the HIV-1 p24 epitopes recognized by PBMC from both HIV-1-positive individuals and HIV-1 p24-vaccinated cats, understand the molecular basis of such common recognition, and evaluate if such peptides are important for eliciting vaccine protection against FIV and against SIV as a model for future human vaccine studies. These studies are the first steps toward identifying conserved protective epitopes that can prevent HIV-1 infection of humans. The innovation of the proposed studies lies in the use of the HIV/FIV-cat model to identify the cross-protective epitopes that can be used as part of HIV-1 vaccine.

描述（由申请人提供）：我们实验室中的最新发现表明，77-78％的无病原体（SPF）猫被进枝B HIV-1/UCD1疫苗免疫的猫受到了随后的FIV感染的保护。基于HIV-1/UCD1和FIV P24蛋白的序列分析，使用仅由HIV-1 P24蛋白组成的疫苗来实现了对FIV感染的显着保护率，其序列与挑战病毒截然不同。 HIV-1 P24疫苗比从致病性FIV菌株中得出的FIV P24疫苗更有效。实际上，在FIV P24接种猫中观察到了FIV挑战感染的增强。这些发现表明，选择HIV-1免疫原对于开发有效的HIV-1疫苗至关重要。提出了两个具体的目的，以鉴定跨保护HIV-1 P24表位，这些表位可能是人类HIV-1疫苗免疫原子。 特定的目标1将使用HIV/FIV-CAT模型确定HIV-1进化枝B P24上的交叉保护表位，并表征保护性表位引起的免疫力。具体目标2将确定HIV/FIV-CAT模型中鉴定出的保守保护性表位与人类HIV-1疫苗发育的相关性。将进行研究以确定来自HIV-1阳性个体和HIV-1 p24疫苗接种的猫的PBMC识别的HIV-1 P24表位，了解这种共同识别的分子基础，并评估这种肽是否对于为FIV和针对SIV作为对未来人类疫苗的模型提供疫苗的疫苗是否重要。这些研究是识别可以防止人类HIV-1感染的保守保护性表位的第一步。拟议研究的创新在于使用HIV/FIV-CAT模型来识别可以用作HIV-1疫苗一部分的交叉保护表位。