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Congenital CMV and CNS Infection Mechanisms of Protective Immunity

先天性巨细胞病毒和中枢神经系统感染的保护性免疫机制

基本信息

批准号：
10398817
负责人：
William Jarvis Britt
金额：
$ 58.05万
依托单位：
UNIVERSITY OF ALABAMA AT BIRMINGHAM
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-05-13 至 2025-04-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10398817
关键词：
Animal Model Antibodies Antibody Response Antiviral Agents Attenuated Attenuated Vaccines Auditory system Biological Biological Products Birth Brain Brain Diseases Brain Injuries CD8-Positive T-Lymphocytes Central Nervous System Diseases Central Nervous System Infections Child Health Clinical Cochlea Complex Cytomegalovirus Cytomegalovirus Infections Data Development Disease Engineering Fetal Development Fetus Glycoproteins Goals HIV Infections Human Human Characteristics Immune response Immunity Immunologics In Vitro Infant Infection Investigation Kinetics Literature Live Birth Mediating Modeling Morbidity - disease rate Mus Natural History Nature Nervous System Trauma Neuraxis Neurodevelopmental Impairment Outcome Pathogenesis Pregnancy Pregnant Women Prevention Preventive vaccine Reporting Research Role Sample Size Secondary to Symptoms System T-Lymphocyte Testing Translating Transplant Recipients Vaccines Viral Viral Antibodies Viral Vaccines Virion Virus Virus Diseases Woman adaptive immune response adaptive immunity chronic infection congenital cytomegalovirus design disorder prevention env Gene Products experimental study hearing impairment human disease in utero in vitro Assay in vivo infant infection infant outcome intrauterine infection long-term sequelae maternal outcome mouse model neurodevelopment neutralizing antibody offspring prevent primary endpoint response transmission process vaccine development vaccine efficacy vaccine response vaccine trial

项目摘要

Project Summary/Abstract Congenital human cytomegalovirus (HCMV) represents the most common viral infection acquired by the developing fetus. Although most infants infected in-utero do not suffer long term symptoms, approximately 10% can have long term sequelae. Central nervous system (CNS) damage is the singular cause of these long term sequelae. Prevention of CNS infection and disease is the target of current antiviral treatment and has been proposed as a goal of prophylactic vaccines. The pathogenesis of CNS disease in congenitally infected human infants remains undefined and to date studies in animal models of CNS infection by HCMV have provided little information secondary to significant limitations inherent in these models. We have recently developed a murine model of infection of the developing CNS with the related murine CMV that recapitulates many key characteristics of the human disease, including hearing loss that is common in infants with congenital CMV infections. Using this model we propose to define mechanisms of protective antibodies that limit CNS infection and disease. In addition, we will explore the use of engineered viruses that are attenuated in their capacity to cause CNS disease and establish persistent infection to induce protective antibody responses. We anticipate that these studies will identify strategies for development of targeted biologics such as antibodies and attenuated viruses that can provide immunologically mediated protection from CNS infection and damage that can follow congenital HCMV infection. Because of the relatedness between MCMV and HCMV, these strategies could be rapidly transitioned into development of similar biologics for human use.

项目总结/摘要先天性人巨细胞病毒（HCMV）是最常见的病毒感染由发育中的胎儿获得。虽然大多数在子宫内感染的婴儿不会遭受长期症状，约10%可有长期后遗症。中枢神经中枢神经系统（CNS）损伤是这些长期后遗症的唯一原因。预防 CNS感染和疾病是目前抗病毒治疗的目标，作为预防性疫苗的目标。中枢神经系统疾病的发病机制先天性感染的人类婴儿仍然不确定，迄今为止在动物中的研究 HCMV的CNS感染模型提供的继发于这些模型中固有的重大局限性。我们最近培育了一种发育中CNS感染相关鼠CMV的模型，人类疾病的许多关键特征，包括听力损失，先天性CMV感染的婴儿。使用这个模型，我们建议定义限制CNS感染和疾病的保护性抗体机制。另外我们将探索使用基因工程病毒， CNS疾病和建立持续感染以诱导保护性抗体应答。我们预计，这些研究将确定发展有针对性的战略，生物制剂，如抗体和减毒病毒，可以提供免疫介导的保护免受先天性HCMV引起的CNS感染和损伤感染由于MCMV和HCMV之间的相关性，这些策略可以迅速过渡到开发类似的人类生物制剂。

项目成果

期刊论文数量（23）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Congenital cytomegalovirus infection as a cause of sensorineural hearing loss in a highly immune population.

DOI：
10.1097/inf.0b013e31822d9640
发表时间：
2011-12
期刊：
The Pediatric infectious disease journal
影响因子：
0
作者：
Yamamoto AY;Mussi-Pinhata MM;Isaac Mde L;Amaral FR;Carvalheiro CG;Aragon DC;Manfredi AK;Boppana SB;Britt WJ
通讯作者：
Britt WJ

Cytomegalovirus Infection: Mouse Model.

DOI：
10.1002/cpim.51
发表时间：
2018-08
期刊：
Current protocols in immunology
影响因子：
0
作者：
Brizić I;Lisnić B;Brune W;Hengel H;Jonjić S
通讯作者：
Jonjić S

Glucocorticoid treatment of MCMV infected newborn mice attenuates CNS inflammation and limits deficits in cerebellar development.

对感染 MCMV 的新生小鼠进行糖皮质激素治疗可减轻中枢神经系统炎症并限制小脑发育缺陷。

DOI：
10.1371/journal.ppat.1003200
发表时间：
2013-03
期刊：
PLoS pathogens
影响因子：
6.7
作者：
Kosmac K;Bantug GR;Pugel EP;Cekinovic D;Jonjic S;Britt WJ
通讯作者：
Britt WJ

SARS-CoV-2 Spike Protein Is Capable of Inducing Cell-Cell Fusions Independent from Its Receptor ACE2 and This Activity Can Be Impaired by Furin Inhibitors or a Subset of Monoclonal Antibodies.

DOI：
10.3390/v15071500
发表时间：
2023-07-04
期刊：
Viruses
影响因子：
0
作者：
Reuter N;Chen X;Kropff B;Peter AS;Britt WJ;Mach M;Überla K;Thomas M
通讯作者：
Thomas M

Birth prevalence and natural history of congenital cytomegalovirus infection in a highly seroimmune population.

DOI：
10.1086/600882
发表时间：
2009-08-15
期刊：
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
影响因子：
0
作者：
Mussi-Pinhata MM;Yamamoto AY;Moura Brito RM;de Lima Isaac M;de Carvalho e Oliveira PF;Boppana S;Britt WJ
通讯作者：
Britt WJ