先天性巨细胞病毒传播的动物模型：对疫苗开发的启示
Animal Models of Congenital Cytomegalovirus Transmission: Implications for Vaccine Development.
作者信息
Roark Hunter K, Jenks Jennifer A, Permar Sallie R, Schleiss Mark R
机构信息
Duke Human Vaccine Institute, Duke University Medical Center, Durham, North Carolina, USA.
Center for Infectious Diseases and Microbiology Translational Research, University of Minnesota Medical School, Department of Pediatrics, Division of Pediatric Infectious Diseases and Immunology, Minneapolis, Minnesota, USA.
出版信息
J Infect Dis. 2020 Mar 5;221(Suppl 1):S60-S73. doi: 10.1093/infdis/jiz484.
Abstract
Although cytomegaloviruses (CMVs) are species-specific, the study of nonhuman CMVs in animal models can help to inform and direct research aimed at developing a human CMV (HCMV) vaccine. Because the driving force behind the development of HCMV vaccines is to prevent congenital infection, the animal model in question must be one in which vertical transmission of virus occurs to the fetus. Fortunately, two such animal models-the rhesus macaque CMV and guinea pig CMV-are characterized by congenital infection. Hence, each model can be evaluated in "proof-of-concept" studies of preconception vaccination aimed at blocking transplacental transmission. This review focuses on similarities and differences in the respective model systems, and it discusses key insights from each model germane to the study of HCMV vaccines.
摘要
尽管巨细胞病毒（CMV）具有种属特异性，但在动物模型中对非人CMV的研究有助于为开发人类巨细胞病毒（HCMV）疫苗的研究提供信息并加以指导。由于开发HCMV疫苗背后的驱动力是预防先天性感染，因此所讨论的动物模型必须是病毒能够垂直传播给胎儿的模型。幸运的是，两种这样的动物模型——恒河猴CMV和豚鼠CMV——都具有先天性感染的特征。因此，在旨在阻断胎盘传播的孕前疫苗接种的“概念验证”研究中，可以对每个模型进行评估。本综述重点关注各个模型系统的异同，并讨论每个模型与HCMV疫苗研究相关的关键见解。
相似文献
1
Animal Models of Congenital Cytomegalovirus Transmission: Implications for Vaccine Development.先天性巨细胞病毒传播的动物模型：对疫苗开发的启示
J Infect Dis. 2020 Mar 5;221(Suppl 1):S60-S73. doi: 10.1093/infdis/jiz484.
2
Neutralization of rhesus cytomegalovirus IL-10 reduces horizontal transmission and alters long-term immunity.中和恒河猴巨细胞病毒的白细胞介素-10 可减少水平传播并改变长期免疫。
Proc Natl Acad Sci U S A. 2019 Jun 25;116(26):13036-13041. doi: 10.1073/pnas.1903317116. Epub 2019 Jun 12.
3
Maternal immune correlates of protection against placental transmission of cytomegalovirus.母体免疫对巨细胞病毒经胎盘传播的保护作用相关因素。
Placenta. 2017 Dec;60 Suppl 1(Suppl 1):S73-S79. doi: 10.1016/j.placenta.2017.04.011. Epub 2017 Apr 20.
4
An attenuated cytomegalovirus vaccine with a deletion of a viral chemokine gene is protective against congenital CMV transmission in a guinea pig model.一种缺失病毒趋化因子基因的减毒巨细胞病毒疫苗在豚鼠模型中可预防先天性巨细胞病毒传播。
Clin Dev Immunol. 2013;2013:906948. doi: 10.1155/2013/906948. Epub 2013 Aug 20.
5
Vaccination with a Live Attenuated Cytomegalovirus Devoid of a Protein Kinase R Inhibitory Gene Results in Reduced Maternal Viremia and Improved Pregnancy Outcome in a Guinea Pig Congenital Infection Model.在豚鼠先天性感染模型中，接种缺乏蛋白激酶R抑制基因的减毒活巨细胞病毒可降低母体病毒血症并改善妊娠结局。
J Virol. 2015 Oct;89(19):9727-38. doi: 10.1128/JVI.01419-15. Epub 2015 Jul 15.
6
A Replication-Defective Human Cytomegalovirus Vaccine Elicits Humoral Immune Responses Analogous to Those with Natural Infection.复制缺陷型人巨细胞病毒疫苗可诱导类似于自然感染的体液免疫应答。
J Virol. 2019 Nov 13;93(23). doi: 10.1128/JVI.00747-19. Print 2019 Dec 1.
7
Comparison of monovalent glycoprotein B with bivalent gB/pp65 (GP83) vaccine for congenital cytomegalovirus infection in a guinea pig model: Inclusion of GP83 reduces gB antibody response but both vaccine approaches provide equivalent protection against pup mortality.在豚鼠模型中，单价糖蛋白B与二价gB/pp65（GP83）疫苗对先天性巨细胞病毒感染的比较：包含GP83会降低gB抗体反应，但两种疫苗方法对幼崽死亡率提供同等保护。
Vaccine. 2015 Jul 31;33(32):4013-8. doi: 10.1016/j.vaccine.2015.06.019. Epub 2015 Jun 13.
8
Animal models of congenital cytomegalovirus infection: an overview of progress in the characterization of guinea pig cytomegalovirus (GPCMV).先天性巨细胞病毒感染的动物模型：豚鼠巨细胞病毒（GPCMV）特征研究进展综述
J Clin Virol. 2002 Aug;25 Suppl 2:S37-49. doi: 10.1016/s1386-6532(02)00100-2.
9
Reduced congenital cytomegalovirus (CMV) infection after maternal immunization with a guinea pig CMV glycoprotein before gestational primary CMV infection in the guinea pig model.在豚鼠模型中，妊娠原发性巨细胞病毒（CMV）感染前用豚鼠CMV糖蛋白对母体进行免疫后，先天性CMV感染减少。
J Infect Dis. 1995 Nov;172(5):1212-20. doi: 10.1093/infdis/172.5.1212.
10
Prospects of a vaccine for the prevention of congenital cytomegalovirus disease.预防先天性巨细胞病毒病疫苗的前景。
Med Microbiol Immunol. 2016 Dec;205(6):537-547. doi: 10.1007/s00430-016-0472-z. Epub 2016 Aug 12.
引用本文的文献
1
From prototype to outbreak: conserved pathogenesis of Oropouche virus in a novel murine pregnancy model highlights its public health implications.从原型到爆发：新型小鼠妊娠模型中奥罗普切病毒的保守发病机制凸显其公共卫生意义。
bioRxiv. 2025 Aug 2:2025.08.02.668287. doi: 10.1101/2025.08.02.668287.
2
Antiviral Immune Responses Against Murine Cytomegalovirus Induced by an Oral -Based Vaccine Expressing Viral M33 Protein.表达病毒M33蛋白的口服疫苗诱导的针对小鼠巨细胞病毒的抗病毒免疫反应
Microorganisms. 2025 Jun 28;13(7):1510. doi: 10.3390/microorganisms13071510.
3
Modeling Virus-Associated Central Nervous System Disease in Non-Human Primates.在非人灵长类动物中模拟病毒相关的中枢神经系统疾病
Int J Mol Sci. 2025 Jul 17;26(14):6886. doi: 10.3390/ijms26146886.
4
Beyond hearing loss: exploring neurological and neurodevelopmental sequelae in asymptomatic congenital cytomegalovirus infection.听力损失之外：探索无症状先天性巨细胞病毒感染中的神经学和神经发育后遗症。
Pediatr Res. 2025 Jul 8. doi: 10.1038/s41390-025-04232-5.
5
Replication-deficient whole-virus vaccines against cytomegalovirus induce protective immunity in a guinea pig congenital infection model.针对巨细胞病毒的复制缺陷型全病毒疫苗在豚鼠先天性感染模型中诱导保护性免疫。
J Virol. 2025 Jul 22;99(7):e0020725. doi: 10.1128/jvi.00207-25. Epub 2025 Jun 11.
6
Oral Vaccination with Attenuated Expressing Viral M25 Protein Effectively Protects Mice Against Murine Cytomegalovirus Infection.用表达病毒M25蛋白的减毒活疫苗进行口服接种可有效保护小鼠免受鼠巨细胞病毒感染。
Pathogens. 2025 Mar 25;14(4):314. doi: 10.3390/pathogens14040314.
7
A promising endeavor against human cytomegalovirus: Predominant epitopes-based recombinant subunit vaccine RH.一项针对人巨细胞病毒的有前景的尝试：基于优势表位的重组亚单位疫苗RH。
Virulence. 2025 Dec;16(1):2497903. doi: 10.1080/21505594.2025.2497903. Epub 2025 May 5.
8
Cytomegalovirus host receptor expression in the human fetal inner ear.巨细胞病毒宿主受体在人胎儿内耳中的表达。
PLoS One. 2025 Mar 31;20(3):e0320605. doi: 10.1371/journal.pone.0320605. eCollection 2025.
9
Why Are Cytomegalovirus-Encoded G-Protein-Coupled Receptors Essential for Infection but Only Variably Conserved?为何巨细胞病毒编码的G蛋白偶联受体对感染至关重要但保守性却存在差异？
Pathogens. 2025 Mar 3;14(3):245. doi: 10.3390/pathogens14030245.
10
The pentameric complex is not required for congenital CMV transmission in seronegative rhesus macaques.对于血清阴性的恒河猴而言，先天性巨细胞病毒传播并不需要五聚体复合物。
Sci Transl Med. 2025 Mar 12;17(789):eadm8961. doi: 10.1126/scitranslmed.adm8961.
本文引用的文献
1
Inclusion of the Viral Pentamer Complex in a Vaccine Design Greatly Improves Protection against Congenital Cytomegalovirus in the Guinea Pig Model.将病毒五聚体复合物纳入疫苗设计可极大提高豚鼠模型中针对先天性巨细胞病毒的保护作用。
J Virol. 2019 Oct 29;93(22). doi: 10.1128/JVI.01442-19. Print 2019 Nov 15.
2
Comparison of vaccination with rhesus CMV (RhCMV) soluble gB with a RhCMV replication-defective virus deleted for MHC class I immune evasion genes in a RhCMV challenge model.在猕猴 CMV（RhCMV）挑战模型中，比较猕猴 CMV（RhCMV）可溶性 gB 疫苗与 MHC I 免疫逃逸基因缺失的 RhCMV 复制缺陷病毒的疫苗接种效果。
Vaccine. 2019 Jan 7;37(2):333-342. doi: 10.1016/j.vaccine.2018.08.043. Epub 2018 Dec 3.
3
Identification and Functional Characterization of a Novel Fc Gamma-Binding Glycoprotein in Rhesus Cytomegalovirus.鉴定并功能表征恒河猴巨细胞病毒中的一种新型 Fcγ 结合糖蛋白。
J Virol. 2019 Feb 5;93(4). doi: 10.1128/JVI.02077-18. Print 2019 Feb 15.
4
Natural history of postnatal rhesus cytomegalovirus shedding by dams and acquisition by infant rhesus monkeys.母猴产后猕猴巨细胞病毒脱落的自然史和幼猴猕猴的获得。
PLoS One. 2018 Oct 24;13(10):e0206330. doi: 10.1371/journal.pone.0206330. eCollection 2018.
5
Using Hysterectomy Rederivation to Produce Guinea Pigs () Free of Guinea Pig Cytomegalovirus.利用子宫切除术再衍生法培育无豚鼠巨细胞病毒的豚鼠
J Am Assoc Lab Anim Sci. 2018 Nov 1;57(6):734-737. doi: 10.30802/AALAS-JAALAS-18-000039. Epub 2018 Oct 10.
6
Tracking KLRC2 (NKG2C)+ memory-like NK cells in SIV+ and rhCMV+ rhesus macaques.追踪 SIV+和 rhCMV+恒河猴中的 KLRC2（NKG2C）+记忆样 NK 细胞。
PLoS Pathog. 2018 May 31;14(5):e1007104. doi: 10.1371/journal.ppat.1007104. eCollection 2018 May.
7
Advancing Our Understanding of Protective Maternal Immunity as a Guide for Development of Vaccines To Reduce Congenital Cytomegalovirus Infections.增进我们对母体保护性免疫的理解，以此作为开发疫苗以减少先天性巨细胞病毒感染的指导。
J Virol. 2018 Mar 14;92(7). doi: 10.1128/JVI.00030-18. Print 2018 Apr 1.
8
Perinatal Outcomes of Non-Primary Maternal Cytomegalovirus Infection: A 15-Year Experience.非原发性母源性巨细胞病毒感染的围产期结局：15年经验总结
Fetal Diagn Ther. 2018;43(2):138-142. doi: 10.1159/000477168. Epub 2017 Jul 12.
9
Preexisting antibodies can protect against congenital cytomegalovirus infection in monkeys.预先存在的抗体可预防猴子的先天性巨细胞病毒感染。
JCI Insight. 2017 Jul 6;2(13). doi: 10.1172/jci.insight.94002.
10
Plasmablast Response to Primary Rhesus Cytomegalovirus (CMV) Infection in a Monkey Model of Congenital CMV Transmission.先天性巨细胞病毒（CMV）传播猴模型中浆母细胞对原发性恒河猴巨细胞病毒（CMV）感染的反应
Clin Vaccine Immunol. 2017 May 5;24(5). doi: 10.1128/CVI.00510-16. Print 2017 May.
Zotero 插件