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

描述（由申请方提供）：我们实验室的最新发现显示，77-78%的无特异性病原体（SPF）猫接种进化枝B HIV-1/UCD 1疫苗后可预防后续FIV感染。基于HIV-1/UCD 1和FIV p24蛋白的序列分析，用仅由HIV-1 p24蛋白组成的疫苗实现了针对FIV感染的显著保护率，所述HIV-1 p24蛋白的序列与攻击病毒如此明显不同。HIV-1 p24疫苗比来源于致病性FIV毒株的FIV p24疫苗更有效。事实上，在FIV p24疫苗接种的猫中观察到FIV攻击感染的增强。这些发现表明，HIV-1免疫原的选择对于开发有效的HIV-1疫苗至关重要。提出了两个具体的目标，以确定交叉保护HIV-1 p24表位，可能是有用的HIV-1疫苗免疫原的人。 具体目标1将使用HIV/FIV-猫模型鉴定HIV-1进化枝B p24上的交叉保护性表位，并表征由保护性表位诱导的免疫。具体目标2将确定在HIV/FIV-猫模型中鉴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HIV-1阳性个体和HIV-1 p24免疫猫的PBMC识别的HIV-1 p24表位，了解这种共同识别的分子基础，并评价这些肽是否对引发疫苗抗FIV和SIV保护作用很重要，作为未来人用疫苗研究的模型。这些研究是确定可以预防人类HIV-1感染的保守保护性表位的第一步。本研究的创新之处在于利用HIV/FIV-cat模型来鉴定可用作HIV-1疫苗一部分的交叉保护性表位。

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.