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

描述(申请人提供)：我们实验室的最新发现表明，77-78%的接种B分支HIV-1/UCD1疫苗的SPF猫可以抵抗后续的FIV感染。根据HIV-1/UCD1和FIV p24蛋白的序列分析，仅由与攻击病毒有明显差异的HIV-1 p24蛋白组成的疫苗对FIV感染具有显著的保护率。HIV-1 p24疫苗的免疫效果优于FIV毒株的p24疫苗。事实上，在接种FIV p24疫苗的猫中观察到了FIV攻击感染的增强。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。提出了两个特定的目标，以确定交叉保护性的HIV-1p24表位，这些表位可能有助于作为人类HIV-1疫苗的免疫原。 具体目的1利用HIV/FIV-CAT模型鉴定HIV-1 B分支p24上的交叉保护表位(S)，并对其诱导的免疫应答进行鉴定。具体目标2将确定HIV/FIV-CAT模型中确定的保守保护性表位与人类HIV-1疫苗开发的相关性。将进行研究，以确定从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，并评估这些肽是否对获得针对FIV和SIV的疫苗保护重要，作为未来人类疫苗研究的模型。这些研究是确定可以预防人类感染HIV-1的保守保护性表位的第一步。拟议研究的创新之处在于使用HIV/FIV-CAT模型来识别可用作HIV-1疫苗一部分的交叉保护表位。

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.