ChAd155 接种狂犬病疫苗与灭活的、纯化的鸡胚细胞狂犬病疫苗在健康成人中的安全性和免疫原性比较

IF 4.5 3区 医学 Q2 IMMUNOLOGY
Varun K. Phadke , Daniel J. Gromer , Paulina A. Rebolledo , Daniel S. Graciaa , Zanthia Wiley , Amy C. Sherman , Erin M. Scherer , Maranda Leary , Tigisty Girmay , Michele P. McCullough , Ji-Young Min , Stefania Capone , Andrea Sommella , Alessandra Vitelli , Jamie Retallick , Janine Seetahal , Mark Koller , Rachel Tsong , Hannah Neill-Gubitz , Mark J. Mulligan , Nadine G. Rouphael
{"title":"ChAd155 接种狂犬病疫苗与灭活的、纯化的鸡胚细胞狂犬病疫苗在健康成人中的安全性和免疫原性比较","authors":"Varun K. Phadke ,&nbsp;Daniel J. Gromer ,&nbsp;Paulina A. Rebolledo ,&nbsp;Daniel S. Graciaa ,&nbsp;Zanthia Wiley ,&nbsp;Amy C. Sherman ,&nbsp;Erin M. Scherer ,&nbsp;Maranda Leary ,&nbsp;Tigisty Girmay ,&nbsp;Michele P. McCullough ,&nbsp;Ji-Young Min ,&nbsp;Stefania Capone ,&nbsp;Andrea Sommella ,&nbsp;Alessandra Vitelli ,&nbsp;Jamie Retallick ,&nbsp;Janine Seetahal ,&nbsp;Mark Koller ,&nbsp;Rachel Tsong ,&nbsp;Hannah Neill-Gubitz ,&nbsp;Mark J. Mulligan ,&nbsp;Nadine G. Rouphael","doi":"10.1016/j.vaccine.2024.126441","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><div>Rabies is a zoonotic viral encephalitis that is endemic in many countries and confers a high mortality. Licensed vaccines require several doses to ensure efficacy. To investigate a logistically favorable approach, we assessed the safety and immunogenicity of ChAd155-RG, a novel investigational rabies vaccine using a replication-defective chimpanzee adenovirus vector.</div></div><div><h3>Methods</h3><div>We conducted a first-in-human, phase 1, randomized, double-blind, dose-escalation trial comparing ChAd155-RG with a licensed inactivated vaccine (RabAvert) in healthy adults. Participants received either RabAvert at standard dosing or ChAd155-RG at a low dose for one immunization or a high dose for one or two immunizations. To assess safety, we evaluated reactogenicity, unsolicited adverse events, and thrombotic events. To measure immunogenicity, we measured rabies viral neutralizing antibody (VNA) titers and anti-ChAd155 neutralizing antibodies.</div></div><div><h3>Results</h3><div>Mild to moderate systemic reactogenicity and transient lymphopenia and neutropenia were more common among recipients of ChAd155-RG compared with those who received RabAvert. No thrombotic events or serious adverse events were reported. Only the groups receiving RabAvert or two doses of high-dose ChAd155-RG achieved 100 % seroconversion, and seroprotection was most durable in the RabAvert group. Most participants had preexisting anti-vector antibodies, which were boosted by ChAd155-RG. Baseline and post-vaccination anti-vector antibody titers were negatively associated with post-vaccination rabies VNA titers.</div></div><div><h3>Conclusions</h3><div>In this phase 1 clinical trial, a novel rabies vaccine using a simian adenovirus vector was safe and tolerable, but generated lower, less durable rabies VNA titers than a standard inactivated rabies virus vaccine, which may be due to preexisting, anti-vector immunity.</div></div>","PeriodicalId":23491,"journal":{"name":"Vaccine","volume":null,"pages":null},"PeriodicalIF":4.5000,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Safety and immunogenicity of a ChAd155-vectored rabies vaccine compared with inactivated, purified chick embryo cell rabies vaccine in healthy adults\",\"authors\":\"Varun K. Phadke ,&nbsp;Daniel J. Gromer ,&nbsp;Paulina A. Rebolledo ,&nbsp;Daniel S. Graciaa ,&nbsp;Zanthia Wiley ,&nbsp;Amy C. Sherman ,&nbsp;Erin M. Scherer ,&nbsp;Maranda Leary ,&nbsp;Tigisty Girmay ,&nbsp;Michele P. McCullough ,&nbsp;Ji-Young Min ,&nbsp;Stefania Capone ,&nbsp;Andrea Sommella ,&nbsp;Alessandra Vitelli ,&nbsp;Jamie Retallick ,&nbsp;Janine Seetahal ,&nbsp;Mark Koller ,&nbsp;Rachel Tsong ,&nbsp;Hannah Neill-Gubitz ,&nbsp;Mark J. Mulligan ,&nbsp;Nadine G. Rouphael\",\"doi\":\"10.1016/j.vaccine.2024.126441\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Background</h3><div>Rabies is a zoonotic viral encephalitis that is endemic in many countries and confers a high mortality. Licensed vaccines require several doses to ensure efficacy. To investigate a logistically favorable approach, we assessed the safety and immunogenicity of ChAd155-RG, a novel investigational rabies vaccine using a replication-defective chimpanzee adenovirus vector.</div></div><div><h3>Methods</h3><div>We conducted a first-in-human, phase 1, randomized, double-blind, dose-escalation trial comparing ChAd155-RG with a licensed inactivated vaccine (RabAvert) in healthy adults. Participants received either RabAvert at standard dosing or ChAd155-RG at a low dose for one immunization or a high dose for one or two immunizations. To assess safety, we evaluated reactogenicity, unsolicited adverse events, and thrombotic events. To measure immunogenicity, we measured rabies viral neutralizing antibody (VNA) titers and anti-ChAd155 neutralizing antibodies.</div></div><div><h3>Results</h3><div>Mild to moderate systemic reactogenicity and transient lymphopenia and neutropenia were more common among recipients of ChAd155-RG compared with those who received RabAvert. No thrombotic events or serious adverse events were reported. Only the groups receiving RabAvert or two doses of high-dose ChAd155-RG achieved 100 % seroconversion, and seroprotection was most durable in the RabAvert group. Most participants had preexisting anti-vector antibodies, which were boosted by ChAd155-RG. Baseline and post-vaccination anti-vector antibody titers were negatively associated with post-vaccination rabies VNA titers.</div></div><div><h3>Conclusions</h3><div>In this phase 1 clinical trial, a novel rabies vaccine using a simian adenovirus vector was safe and tolerable, but generated lower, less durable rabies VNA titers than a standard inactivated rabies virus vaccine, which may be due to preexisting, anti-vector immunity.</div></div>\",\"PeriodicalId\":23491,\"journal\":{\"name\":\"Vaccine\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":4.5000,\"publicationDate\":\"2024-10-16\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Vaccine\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0264410X2401123X\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"IMMUNOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Vaccine","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0264410X2401123X","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
引用次数: 0

摘要

背景狂犬病是一种人畜共患的病毒性脑炎,在许多国家流行,死亡率很高。已获批准的疫苗需要多次接种才能确保疗效。为了研究一种在后勤上有利的方法,我们评估了 ChAd155-RG 的安全性和免疫原性,这是一种使用复制缺陷黑猩猩腺病毒载体的新型狂犬病疫苗。方法我们首次在健康成年人中开展了一项人体1期随机、双盲、剂量递增试验,比较 ChAd155-RG 和已获许可的灭活疫苗(RabAvert)。受试者以标准剂量接种 RabAvert 或以低剂量接种 ChAd155-RG 一次,或以高剂量接种 ChAd155-RG 一次或两次。为了评估安全性,我们评估了致反应性、非主动不良事件和血栓事件。为了评估免疫原性,我们测定了狂犬病病毒中和抗体 (VNA) 滴度和抗 ChAd155 中和抗体。结果与接受 RabAvert 的受试者相比,接受 ChAd155-RG 的受试者更容易出现轻度至中度全身反应原、一过性淋巴细胞减少症和中性粒细胞减少症。没有血栓事件或严重不良事件的报道。只有接受RabAvert或两剂高剂量ChAd155-RG的组别实现了100%的血清转换,而RabAvert组的血清保护最为持久。大多数参与者在接种前已存在抗载体抗体,ChAd155-RG增强了这些抗体。结论在这项 1 期临床试验中,使用猿腺病毒载体的新型狂犬病疫苗是安全和可耐受的,但与标准的狂犬病病毒灭活疫苗相比,该疫苗产生的狂犬病 VNA 滴度较低且不持久,这可能是由于预先存在的抗载体免疫所致。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Safety and immunogenicity of a ChAd155-vectored rabies vaccine compared with inactivated, purified chick embryo cell rabies vaccine in healthy adults

Background

Rabies is a zoonotic viral encephalitis that is endemic in many countries and confers a high mortality. Licensed vaccines require several doses to ensure efficacy. To investigate a logistically favorable approach, we assessed the safety and immunogenicity of ChAd155-RG, a novel investigational rabies vaccine using a replication-defective chimpanzee adenovirus vector.

Methods

We conducted a first-in-human, phase 1, randomized, double-blind, dose-escalation trial comparing ChAd155-RG with a licensed inactivated vaccine (RabAvert) in healthy adults. Participants received either RabAvert at standard dosing or ChAd155-RG at a low dose for one immunization or a high dose for one or two immunizations. To assess safety, we evaluated reactogenicity, unsolicited adverse events, and thrombotic events. To measure immunogenicity, we measured rabies viral neutralizing antibody (VNA) titers and anti-ChAd155 neutralizing antibodies.

Results

Mild to moderate systemic reactogenicity and transient lymphopenia and neutropenia were more common among recipients of ChAd155-RG compared with those who received RabAvert. No thrombotic events or serious adverse events were reported. Only the groups receiving RabAvert or two doses of high-dose ChAd155-RG achieved 100 % seroconversion, and seroprotection was most durable in the RabAvert group. Most participants had preexisting anti-vector antibodies, which were boosted by ChAd155-RG. Baseline and post-vaccination anti-vector antibody titers were negatively associated with post-vaccination rabies VNA titers.

Conclusions

In this phase 1 clinical trial, a novel rabies vaccine using a simian adenovirus vector was safe and tolerable, but generated lower, less durable rabies VNA titers than a standard inactivated rabies virus vaccine, which may be due to preexisting, anti-vector immunity.
求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
Vaccine
Vaccine 医学-免疫学
CiteScore
8.70
自引率
5.50%
发文量
992
审稿时长
131 days
期刊介绍: Vaccine is unique in publishing the highest quality science across all disciplines relevant to the field of vaccinology - all original article submissions across basic and clinical research, vaccine manufacturing, history, public policy, behavioral science and ethics, social sciences, safety, and many other related areas are welcomed. The submission categories as given in the Guide for Authors indicate where we receive the most papers. Papers outside these major areas are also welcome and authors are encouraged to contact us with specific questions.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信