Using the vesicular stomatitis virus vector (rVSV vector) platform for SARS-CoV-2 vaccine development: Phase 1/2 safety and immunogenicity of IIBR-100 in healthy adults

IF 4.5 3区医学 Q2 IMMUNOLOGY

Vaccine Pub Date : 2025-10-16 DOI:10.1016/j.vaccine.2025.127837

Yoseph Caraco , Noa Madar-Balakirski , Eytan Ben-Ami , David Zeltser , Shlomo Maayan , Noa Eliakim-Raz , Avivit Peer , Tal Brosh-Nissimov , Victor Vishlitzky , Adi Beth-Din , Erez Bar-Haim , Tomer Israely , Nir Paran , Morly Fisher , Matti Hoggeg , Jacob Atsmon , Daniel Cohen , Dan Goldstaub , Yotam Levin , Yehuda Danon , Hadar Marcus

{"title":"Using the vesicular stomatitis virus vector (rVSV vector) platform for SARS-CoV-2 vaccine development: Phase 1/2 safety and immunogenicity of IIBR-100 in healthy adults","authors":"Yoseph Caraco , Noa Madar-Balakirski , Eytan Ben-Ami , David Zeltser , Shlomo Maayan , Noa Eliakim-Raz , Avivit Peer , Tal Brosh-Nissimov , Victor Vishlitzky , Adi Beth-Din , Erez Bar-Haim , Tomer Israely , Nir Paran , Morly Fisher , Matti Hoggeg , Jacob Atsmon , Daniel Cohen , Dan Goldstaub , Yotam Levin , Yehuda Danon , Hadar Marcus","doi":"10.1016/j.vaccine.2025.127837","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><div>We investigated the safety and immunogenicity of the IIBR-100 (rVSV-SARS-CoV-2-S) vaccine, a recombinant VSV-ΔG-spike vaccine against SARS-CoV-2 virus.</div></div><div><h3>Methods</h3><div>In a phase 1/2, randomized, observer-blind, placebo-controlled study (<span><span>ClinicalTrials.gov</span><svg><path></path></svg></span>: NCT 04608305), healthy younger (18–55 years) and older (56–85 years) adults were recruited from eight clinical sites in Israel. In the phase 1 study, low (1 × 10<sup>5</sup> PFU), mid (1 × 10<sup>6</sup> PFU), and high doses (1 × 10<sup>7</sup> PFU) of IIBR-100 were tested in a single-dose treatment regimen, with an additional booster dose for the low-dose group only. Based on the phase 1 study results, only mid- and high-dose prime-boost regimens alongside an additional top dose (1 × 10<sup>8</sup> PFU) were tested in the phase 2 study. Participants, randomly assigned to either IIBR-100 or placebo, were followed for 12 months from the last vaccination for safety and immunogenicity outcomes.</div></div><div><h3>Findings</h3><div>No safety concerns were observed in the phase 1 study (<em>N</em> = 82); therefore, the study moved on to phase 2. In phase 2 (<em>N</em> = 762), for both age groups, the most common AEs included injection-site pain (20–64 %), fatigue (21–33 %), and headache (15–22 %). In the top-dose group, neutralizing and binding antibody titers peaked on Days 35 and 42, respectively; seroconversion rates reached maximal levels by Day 56 for neutralizing antibody and binding antibody (spike and RBD).</div></div><div><h3>Interpretation</h3><div>The IIBR-100 vaccine against SARS-CoV-2 in prime-boost regimens at 1 × 10<sup>7</sup> PFU/mL and 1 × 10<sup>8</sup> PFU/mL doses is safe, well tolerated, and immunogenic in healthy adults.</div></div><div><h3>Clinical trial registry</h3><div>This trial is registered at <span><span>ClinicalTrials.gov</span><svg><path></path></svg></span> (NCT 04608305) and in the trial registry of the Israeli Ministry of Health website.</div></div>","PeriodicalId":23491,"journal":{"name":"Vaccine","volume":"67 ","pages":"Article 127837"},"PeriodicalIF":4.5000,"publicationDate":"2025-10-16","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/S0264410X2501134X","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

Abstract

Background

We investigated the safety and immunogenicity of the IIBR-100 (rVSV-SARS-CoV-2-S) vaccine, a recombinant VSV-ΔG-spike vaccine against SARS-CoV-2 virus.

Methods

In a phase 1/2, randomized, observer-blind, placebo-controlled study (ClinicalTrials.gov: NCT 04608305), healthy younger (18–55 years) and older (56–85 years) adults were recruited from eight clinical sites in Israel. In the phase 1 study, low (1 × 10⁵ PFU), mid (1 × 10⁶ PFU), and high doses (1 × 10⁷ PFU) of IIBR-100 were tested in a single-dose treatment regimen, with an additional booster dose for the low-dose group only. Based on the phase 1 study results, only mid- and high-dose prime-boost regimens alongside an additional top dose (1 × 10⁸ PFU) were tested in the phase 2 study. Participants, randomly assigned to either IIBR-100 or placebo, were followed for 12 months from the last vaccination for safety and immunogenicity outcomes.

Findings

No safety concerns were observed in the phase 1 study (N = 82); therefore, the study moved on to phase 2. In phase 2 (N = 762), for both age groups, the most common AEs included injection-site pain (20–64 %), fatigue (21–33 %), and headache (15–22 %). In the top-dose group, neutralizing and binding antibody titers peaked on Days 35 and 42, respectively; seroconversion rates reached maximal levels by Day 56 for neutralizing antibody and binding antibody (spike and RBD).

Interpretation

The IIBR-100 vaccine against SARS-CoV-2 in prime-boost regimens at 1 × 10⁷ PFU/mL and 1 × 10⁸ PFU/mL doses is safe, well tolerated, and immunogenic in healthy adults.

Clinical trial registry

This trial is registered at ClinicalTrials.gov (NCT 04608305) and in the trial registry of the Israeli Ministry of Health website.

查看原文本刊更多论文

利用水疱性口炎病毒载体（rVSV载体）平台开发SARS-CoV-2疫苗：IIBR-100在健康成人中的1/2期安全性和免疫原性

背景：我们研究了针对SARS-CoV-2病毒的重组VSV-ΔG-spike疫苗ibr -100 （rVSV-SARS-CoV-2-S）疫苗的安全性和免疫原性。方法：在一项1/2期、随机、观察者盲、安慰剂对照研究（ClinicalTrials.gov: NCT04608305）中，从以色列的8个临床站点招募了健康的年轻人（18-55岁）和老年人（56-85岁）。在i期研究中，低剂量（1 × 105 PFU）、中剂量（1 × 106 PFU）和高剂量（1 × 107 PFU）的IIBR-100在单剂量治疗方案中进行了测试，仅为低剂量组增加了额外的加强剂量。基于1期研究结果，仅在2期研究中测试了中剂量和高剂量初始-增强方案以及额外的最高剂量（1 × 108 PFU）。随机分配到ibrr -100或安慰剂组的参与者，从最后一次接种疫苗开始随访12个月，以观察安全性和免疫原性结果。结果：在1期研究中未发现安全性问题（N = 82）；因此，研究进入了第二阶段。在第二阶段（N = 762），两个年龄组最常见的ae包括注射部位疼痛（20- 64%）、疲劳（21- 33%）和头痛（15- 22%）。在最高剂量组，中和抗体滴度和结合抗体滴度分别在第35天和第42天达到峰值；中和抗体和结合抗体（spike和RBD）的血清转化率在第56天达到最高水平。解释：针对SARS-CoV-2的ibr -100疫苗在1 × 107 PFU/mL和1 × 108 PFU/mL剂量的初始-强化方案中是安全的，耐受性良好，并且在健康成人中具有免疫原性。临床试验注册：该试验在ClinicalTrials.gov （NCT04608305）和以色列卫生部网站的试验注册中注册。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

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.