A Mucosal Vaccine for HSV-2

HSV-2 粘膜疫苗

• 批准号: 8034318
• 负责人: Kejian Yang
• 金额: $ 76.3万
• 依托单位: BIOMEDICAL RESEARCH MODELS, INC.
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-04-01 至 2013-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8034318
• 关键词: Adult; American; Animal Model; Antibodies; Antigens; Biological Response Modifiers; Cavia; Centers for Disease Control and Prevention (U.S.); Complement; DNA; DNA Vaccines; Disease; Dose; Drug Formulations; Encapsulated; Encephalitis; Female; Funding; Genital system; Glycoproteins; Goals; HIV; Healthy People 2010; Herpesvirus 1; Human; Human Herpesvirus 2; Human Papillomavirus; Immune; Immune response; Immunity; Immunization; Immunocompromised Host; Immunoglobulin A; Immunoglobulin G; Individual; Infant; Infection; Latent Virus; Lead; Lesion; Liposomes; Longevity; Marketing; Medical; Minor; Modeling; Morbidity - disease rate; Mothers; Mus; Organ; Pain; Patients; Phase; Population; Preparation; Protocols documentation; Public Health; Publications; Quality Control; Secretory Immunoglobulin A; Serum; Sexually Transmitted Diseases; Simplexvirus; Small Business Innovation Research Grant; Surface; Symptoms; T cell response; Testing; Time; Titrations; Toxicity Tests; United States Public Health Service; Vaccinated; Vaccination; Vaccines; Vagina; Vertical Disease Transmission; Viral; Viral Encephalitis; Virus; Visceral; cofactor; cost; disorder prevention; genital infection; mouse model; mucosal vaccine; novel; novel vaccines; pathogen; preclinical safety; prevent; prophylactic; psychologic; public health relevance; research study; response; safety testing; success; vaccine candidate; vaccine efficacy

DESCRIPTION (provided by applicant): Approximately 1 out of every 5 Americans is infected with herpes simplex virus type 2 (HSV-2). Localized genital infection by HSV-2 results in painful recurring genital lesions while disseminated infection can involve multiple visceral organs and lethal encephalitis. Using Phase 1 funding we have developed a new heterologous immunization protocol composed of a glycoprotein D (gD) DNA vaccine followed by a liposome-encapsulated gD boost. This protocol induces robust serum IgG antigen-specific antibodies, mucosal IgG and secretory IgA and a T helper type 1 (Th1)-biased immune response. Mice immunized with this protocol are protected from disease after infection with 100 times the lethal dose of virus. Use of a higher priming dose of DNA revealed sterilizing immunity in 80% of immunized mice. We are requesting Phase 2 funding to complement and extend the studies in preparation for preclinical safety testing. The requested funding will be used to further characterize immune mediators induced by the novel HSV-2 vaccine. Funding will also be used to evaluate commercial suppliers of vaccine components and establish quality control parameters. Dosing of components will be further optimized in preparation for human use and toxicity testing. Guinea pigs will be used to demonstrate efficacy of the vaccine in a second animal model and to test the ability of the vaccine to prevent establishment of latency and/or reactivation of latent virus. The end result of these experiments will be the establishment of a novel vaccine for HSV-2. PUBLIC HEALTH RELEVANCE: This vaccine would clearly have an impact on the greater than $1.6 billion spent annually on direct medical costs associated with HSV-2. The Public Health Service (PHS) has recognized the significant public health issues caused by herpes simplex virus. The PHS publication, "Healthy People 2010", has set sexually transmitted diseases as a national priority with a goal to reduce the number of adults infected with human papilloma virus and HSV-2.

描述（由申请人提供）：大约每5个美国人中就有1个感染了2型单纯疱疹病毒（HSV-2）。HSV-2的局部生殖器感染导致疼痛的复发性生殖器病变，而播散性感染可累及多个内脏器官和致命的脑炎。利用第1阶段资金，我们开发了一种新的异源免疫方案，由糖蛋白D（gD）DNA疫苗和脂质体包封的gD加强免疫组成。该方案诱导强大的血清IgG抗原特异性抗体，粘膜IgG和分泌型伊加和辅助性T细胞1型（Th 1）偏向的免疫应答。用该方案免疫的小鼠在用100倍致死剂量的病毒感染后免受疾病的影响。使用更高的启动剂量的DNA显示在80%的免疫小鼠的绝育免疫。我们正在申请2期资金，以补充和扩展临床前安全性测试的研究。申请的资金将用于进一步表征新型HSV-2疫苗诱导的免疫介质。资金还将用于评估疫苗成分的商业供应商，并确定质量控制参数。将进一步优化组分的剂量，以备人类使用和毒性试验。豚鼠将用于证明疫苗在第二种动物模型中的有效性，并检测疫苗预防潜伏期建立和/或潜伏病毒再活化的能力。这些实验的最终结果将是建立一种新的HSV-2疫苗。公共卫生关系：这种疫苗显然将对每年用于与HSV-2相关的直接医疗费用超过16亿美元产生影响。公共卫生服务（PHS）已经认识到由单纯疱疹病毒引起的重大公共卫生问题。公共卫生协会出版物《2010年健康人》将性传播疾病定为国家优先事项，目标是减少感染人类乳头瘤病毒和HSV-2的成年人人数。