An experimental mRNA vaccine against human cytomegalovirus (CMV), a common virus that can infect babies during pregnancy, elicited some of the most promising immune responses to date of any CMV vaccine candidate, according to a study by Weill Cornell Medicine investigators.

威尔·康奈尔医学研究人员的一项研究表明，一种针对人类巨细胞病毒（CMV）的实验性mRNA疫苗引发了迄今为止所有CMV候选疫苗中最有希望的免疫反应。CMV是一种常见的病毒，可在怀孕期间感染婴儿。

The study, published in the Journal of Infectious Diseases on Feb. 7, provided evidence that the new mRNA vaccine candidate, which is manufactured by Moderna, Inc., may protect adults against CMV. Thus, it could potentially prevent women from passing the harmful infection to their babies during pregnancy.

这项研究发表在2月7日的《传染病杂志》上，提供的证据表明，由Moderna，Inc.生产的新型mRNA候选疫苗可以保护成年人免受CMV的侵害。因此，它有可能防止女性在怀孕期间将有害感染传播给婴儿。

Compared with a previous moderately successful vaccine candidate called gB/MF59, the mRNA vaccine elicited responses that were better at preventing the CMV virus from infecting epithelial cells that line the mouth and nose and provide the first line of defense against viral infection. The mRNA vaccine was also more effective at triggering the immune system to destroy CMV-infected cells. .

与之前一种名为gB/MF59的中等成功候选疫苗相比，mRNA疫苗引发的反应更能防止CMV病毒感染口腔和鼻子的上皮细胞，并提供抵抗病毒感染的第一道防线。mRNA疫苗在触发免疫系统破坏CMV感染细胞方面也更有效。。。

'We learned that the newer vaccine has the potential to be more effective than a previous CMV vaccine candidate because some of the functional immune responses it elicits are higher in magnitude,' said senior author Dr. Sallie Permar, the chair of the Department of Pediatrics and Nancy C. Paduano Professor in Pediatrics at Weill Cornell Medicine.

资深作者、儿科系主任萨利·佩马尔（SalliePermar）博士和威尔·康奈尔医学院（WeillCornellMedicine）儿科教授南希·帕杜阿诺（NancyC.Paduano）说：“我们了解到，新疫苗有可能比以前的CMV候选疫苗更有效，因为它引发的一些功能性免疫反应幅度更大。”。

'An ongoing clinical trial will confirm if those differences lead to greater protection against CMV infection.' .

“一项正在进行的临床试验将证实这些差异是否会对CMV感染产生更大的保护作用。”。。

Though healthy adults are largely asymptomatic, one in every 200 newborns worldwide are infected with CMV during their mother’s pregnancy. The virus rarely causes serious illness in healthy adults, but it can cause birth defects and brain damage in newborns infected in utero and deadly infections in immune-compromised adults. .

尽管健康成年人基本上没有症状，但全世界每200名新生儿中就有一名在母亲怀孕期间感染了巨细胞病毒。该病毒很少在健康成年人中引起严重疾病，但它可以在子宫内感染的新生儿中引起出生缺陷和脑损伤，并在免疫缺陷的成年人中引起致命感染。。。

'It is the most common congenital infection worldwide,' explained Dr. Permar, who is also pediatrician-in-chief at NewYork-Presbyterian/Weill Cornell Medical Center and NewYork-Presbyterian Komansky Children's Hospital.

“这是全世界最常见的先天性感染，”Permar博士解释道，他也是纽约长老会/威尔康奈尔医学中心和纽约长老会科曼斯基儿童医院的儿科医生。

Co-first authors Dr. Krithika P. Karthigeyan, postdoctoral associate in pediatrics at Weill Cornell Medicine, and Dr. Xintao Hu, who was part of the research team at the time, also contributed to this research.

第一作者之一、威尔·康奈尔医学院儿科博士后助理Krithika P.Karthigeyan博士和当时参与研究团队的Xintao Hu博士也为这项研究做出了贡献。

CMV Vaccine Candidates

巨细胞病毒候选疫苗

Previously, Sanofi and Novartis had developed vaccine candidate gB/MF59, which targeted glycoprotein B (gB), a sugar-laden viral surface protein that works with other proteins to help CMV attach to and enter human cells. It protected about half of vaccinated individuals from CMV infection in a phase 2 clinical trial led by the National Institute of Allergy and Infectious Diseases Vaccine Clinical Trials Network.

此前，赛诺菲（Sanofi）和诺华（Novartis）开发了候选疫苗gB/MF59，该疫苗靶向糖蛋白B（gB），一种含糖的病毒表面蛋白，可与其他蛋白质一起帮助CMV附着并进入人类细胞。在国家过敏与传染病疫苗临床试验网络领导的第二阶段临床试验中，它保护了大约一半接种疫苗的个体免受CMV感染。

When the trial ended in 2013, it did not progress to phase 3 clinical trials. .

当试验于2013年结束时，它没有进展到3期临床试验。。。

Dr. Permar and her colleagues used the data and patient samples from the gB/MF59 phase 2 trial in adolescent girls as a benchmark to assess the new mRNA-based vaccine. Using the same technology that produced the company's COVID-19 vaccine, Moderna's CMV vaccine added a second target - a five-unit protein complex that allows the virus to infect the epithelial cells that line the nose and mouth - in addition to glycoprotein B. .

Permar博士和她的同事使用gB/MF59青春期女孩2期试验的数据和患者样本作为评估新的基于mRNA的疫苗的基准。使用与生产该公司新型冠状病毒疫苗相同的技术，Moderna的巨细胞病毒疫苗除了糖蛋白B之外，还添加了第二个靶标-一种五单位蛋白质复合物，可以使病毒感染鼻子和口腔的上皮细胞。。。

In this study, Dr. Permar and her team compared the immune responses of individuals vaccinated with gB/MF59 in the phase 2 trial with those immunized with Moderna’s mRNA-based CMV vaccine in a phase 1 clinical trial which ended in 2020. Specifically, the team compared the immune responses in people who were protected against CMV infection after receiving the older vaccine. .

在这项研究中，Permar博士和她的团队比较了在第二阶段试验中接种gB/MF59疫苗的个体与在2020年结束的第一阶段临床试验中接种Moderna基于mRNA的CMV疫苗的个体的免疫反应。具体来说，该团队比较了接受较旧疫苗后受到CMV感染保护的人群的免疫反应。。。

New Vaccine Triggers Stronger Immune Response

新疫苗引发更强的免疫反应

The mRNA vaccine - likely because of the additional second target - did a better job of preventing the CMV virus from infecting healthy epithelial cells. The vaccine triggered immune cells to produce neutralizing antibodies that block the entry of the virus into a cell, which prevents viral replication.

mRNA疫苗-可能是因为另外的第二个靶标-在防止CMV病毒感染健康上皮细胞方面做得更好。该疫苗触发免疫细胞产生中和抗体，阻止病毒进入细胞，从而阻止病毒复制。

Also, the mRNA vaccine induced antibody responses that could destroy infected cells. In contrast, people vaccinated with the gB/MF59 vaccine produced higher levels of antibodies against gB that had low neutralizing activity but had strong ability to engulf and eliminate a virus. .

此外，mRNA疫苗诱导的抗体反应可能会破坏受感染的细胞。相比之下，接种gB/MF59疫苗的人产生更高水平的抗gB抗体，其中和活性低，但吞噬和消除病毒的能力强。。。

The Moderna vaccine has moved on to the first ever phase 3 clinical study for a CMV vaccine candidate, which will help determine if these differences in immune responses will lead to stronger protection against CMV. 'After more than 50 years of research, we are closer than ever to having a licensed CMV vaccine,' Dr.

Moderna疫苗已经进入有史以来第一个针对巨细胞病毒候选疫苗的3期临床研究，这将有助于确定这些免疫反应的差异是否会导致对巨细胞病毒的更强保护经过50多年的研究，我们比以往任何时候都更接近获得许可的巨细胞病毒疫苗。

Permar said. 'The new mRNA platform has a lot of potential.' .

佩马尔说新的mRNA平台具有很大的潜力。”。。

In the meantime, Dr. Permar and her colleagues have developed a preclinical model to test whether similar vaccines protect against fetal CMV transmission during pregnancy.

与此同时，Permar博士和她的同事开发了一种临床前模型，以测试类似疫苗是否可以预防怀孕期间胎儿巨细胞病毒的传播。

Hu X, Karthigeyan KP, Herbek S, Valencia SM, Jenks JA, Webster H, Miller IG, Connors M, Pollara J, Andy C, Gerber LM, Walter EB, Edwards KM, Bernstein DI, Hou J, Koch M, Panther L, Carfi A, Wu K, Permar SR.

胡X，Karthigeyan KP，Herbek S，Valencia SM，Jenks JA，Webster H，Miller IG，Connors M，Pollara J，Andy C，Gerber LM，Walter EB，Edwards KM，Bernstein DI，Hou J，Koch M，Panther L，Carfi A，Wu K，Permar SR。

Human Cytomegalovirus mRNA-1647 Vaccine Candidate Elicits Potent and Broad Neutralization and Higher Antibody-Dependent Cellular Cytotoxicity Responses Than the gB/MF59 Vaccine.

与gB/MF59疫苗相比，人巨细胞病毒mRNA-1647候选疫苗引发有效和广泛的中和作用以及更高的抗体依赖性细胞毒性反应。

J Infect Dis. 2024 Feb 7:jiad593. doi: 10.1093/infdis/jiad593

J感染疾病。2024年2月7日：jiad593。doi:10.1093/infdis/jiad593