HETEROCONJUGATE VACCINES AGAINST HERPES SIMPLEX VIRUS

该项目的主要目标是开发L.E.A.P.S.（TM）抗单纯疱疹病毒的异偶联肽疫苗，以预防或治疗人类感染。异偶联疫苗是由含有确定的T细胞表位的肽和预测能与T细胞或抗原提呈细胞结合的肽构成的。正在使用的T细胞表位来自HSV-1的ICP27、糖蛋白B和糖蛋白D。我们的I期研究证明了这项新技术背后的原理，表明将病毒肽表位结合到基于L.E.A.P.S.结构的疫苗中可以增强和确定免疫反应的类型，从而促进保护性而非有害免疫反应的发展。然后，L.E.A.P.S.疫苗可以用与佐剂组装的LEAPS构建物配制，对确定的表位产生确定的免疫反应。II期研究的主要目标是优化L.E.A.P.S.肽（或混合物）、佐剂和其他成分的疫苗配方，以便进行人体试验。此外，我们将研究L.E.A.P.S.肽增强免疫反应的作用机制。单纯疱疹病毒疫苗也是开发异偶联疫苗的原型，用于治疗或预防由其他传染性病原体引起的疾病。我们研究的最终目标是获得足够的数据，以便进行人体试验。建议的商业应用：异偶联肽疫苗使用称为L.E.A.P.S.（配体表位抗原呈递系统）的专有新技术来治疗和/或预防单纯疱疹病毒（HSV）感染和疾病。单纯疱疹病毒是一种常见的口腔病原体和性传播疾病，也会引起严重的疾病。估计有4000万到6000万美国人感染了HSV，每年大约有60万新病例发生。单纯疱疹病毒疫苗将成为开发异偶联疫苗的原型，用于治疗或预防由其他传染因子引起的疾病。

The primary goal of this program is the development of L.E.A.P.S.(TM) heteroconjugate peptide vaccines against herpes simplex virus) to prevent or treat human infection. The heteroconjugate vaccines are constructed of peptides which contain defined T cell epitopes and peptides which are predicted to bind to T cells or antigen presenting cells. The T cell epitopes that are being used are from the ICP27, glycoprotein B, and glycoprotein D of HSV-1. Our Phase I studies proved the principle behind this new technology by showing that incorporation of a viral peptide epitope into a L.E.A.P.S. construct based vaccine can enhance and define the type of immune response which is elicited to promote the development of protective and not detrimental immune responses. A L.E.A.P.S. vaccine can then be formulation with LEAPS constructs assembled with adjuvants to produce defined immune responses to defined epitopes. The major goal of the Phase II studies will be to optimize the vaccine formulation with respect to L.E.A.P.S. peptide (or mixture), the adjuvant and other components to allow progression to human trials. In addition, we will study the mechanism of action by which the L.E.A.P.S. peptide potentiates the immune response. The HSV vaccines are also prototypes for the development of heteroconjugate vaccine to treat or prevent disease caused by other infectious agents. The ultimate goal of our study will be to develop sufficient data to allow progression to human trials. PROPOSED COMMERCIAL APPLICATION: Heteroconjugate peptide vaccines use proprietary new technology called L.E.A.P.S. (Ligand Epitope Antigen Presentation System) to provide treatment and/or prophlysis against herpes simplex virus (HSV) infection and disease. HSV is a common oral pathogen and sexually transmitted disease which also causes serious disease. An estimated 40 to 60 million Americans are infected with HSV with approximately 600,000 new cases occurring per year. The HSV vaccine will be prototypes for the development of heteroconjugate vaccines to treat or prevent disease by other infectious agents.