Pitisuttithum Punnee, Luvira Viravarn, Lawpoolsri Saranath, Muangnoicharoen Sant, Kamolratanakul Supitcha, Sivakorn Chaisith, Narakorn Piengthong, Surichan Somchaiya, Prangpratanporn Sumalee, Puksuriwong Suttida, Lamola Steven, Mercer Laina D, Raghunandan Rama, Sun Weina, Liu Yonghong, Carreño Juan Manuel, Scharf Rami, Phumratanaprapin Weerapong, Amanat Fatima, Gagnon Luc, Hsieh Ching-Lin, Kaweepornpoj Ruangchai, Khan Sarwat, Lal Manjari, McCroskery Stephen, McLellan Jason, Mena Ignacio, Meseck Marcia, Phonrat Benjaluck, Sabmee Yupa, Singchareon Ratsamikorn, Slamanig Stefan, Suthepakul Nava, Tcheou Johnstone, Thantamnu Narumon, Theerasurakarn Sompone, Tran Steven, Vilasmongkolchai Thanakrit, White Jessica A, Garcia-Sastre Adolfo, Palese Peter, Krammer Florian, Poopipatpol Kittisak, Wirachwong Ponthip, Hjorth Richard, Innis Bruce L
medRxiv. 2021 Sep 22:2021.09.17.21263758. doi: 10.1101/2021.09.17.21263758.
Production of affordable coronavirus disease 2019 (COVID-19) vaccines in low- and middle-income countries is needed. NDV-HXP-S is an inactivated egg-based Newcastle disease virus vaccine expressing the spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It's being developed in Thailand, Vietnam, and Brazil; herein are initial results from Thailand.
This phase 1 stage of a randomised, dose-escalation, observer-blind, placebo-controlled, phase 1/2 trial was conducted at the Vaccine Trial Centre, Mahidol University (Bangkok). Healthy adults aged 18-59 years, non-pregnant and negative for SARS-CoV-2 antibodies were eligible. Participants were block randomised to receive one of six treatments by intramuscular injection twice, 28 days apart: 1 µg±CpG1018 (a toll-like receptor 9 agonist), 3 µg±CpG1018, 10 µg, or placebo. Participants and personnel assessing outcomes were masked to treatment. The primary outcomes were solicited and spontaneously reported adverse events (AEs) during 7 and 28 days after each vaccination, respectively. Secondary outcomes were immunogenicity measures (anti-S IgG and pseudotyped virus neutralisation). An interim analysis assessed safety at day 57 in treatment-exposed individuals and immunogenicity through day 43 per protocol. ClinicalTrials.gov ( NCT04764422 ).
Between March 20 and April 23, 2021, 377 individuals were screened and 210 were enrolled (35 per group); all received dose one; five missed dose two. The most common solicited AEs among vaccinees, all predominantly mild, were injection site pain (<63%), fatigue (<35%), headache (<32%), and myalgia (<32%). The proportion reporting a vaccine-related AE ranged from 5·7% to 17·1% among vaccine groups and was 2·9% in controls; there was no vaccine-related serious adverse event. The 10 µg formulation's immunogenicity ranked best, followed by 3 µg+CpG1018, 3 µg, 1 µg+CpG1018, and 1 µg formulations. On day 43, the geometric mean concentrations of 50% neutralising antibody ranged from 122·23 IU/mL (1 µg, 95% CI 86·40-172·91) to 474·35 IU/mL (10 µg, 95% CI 320·90-701·19), with 93·9% to 100% of vaccine groups attaining a ≥4-fold increase over baseline.
NDV-HXP-S had an acceptable safety profile and potent immunogenicity. The 3 µg and 3 µg+CpG1018 formulations advanced to phase 2.
National Vaccine Institute (Thailand), National Research Council (Thailand), Bill & Melinda Gates Foundation, National Institutes of Health (USA).
低收入和中等收入国家需要生产价格可承受的2019冠状病毒病（COVID-19）疫苗。NDV-HXP-S是一种基于鸡蛋的新城疫病毒灭活疫苗，表达严重急性呼吸综合征冠状病毒2（SARS-CoV-2）的刺突蛋白。该疫苗正在泰国、越南和巴西研发；本文介绍泰国的初步结果。
本研究为一项随机、剂量递增、观察者盲法、安慰剂对照的1/2期试验的1期阶段，在玛希隆大学疫苗试验中心（曼谷）进行。纳入年龄在18至59岁之间、非妊娠且SARS-CoV-2抗体阴性的健康成年人。参与者被区组随机分组，通过肌肉注射分两次接种六种治疗方案之一，每次间隔28天：1 μg±CpG1018（一种Toll样受体9激动剂）、3 μg±CpG1018、10 μg或安慰剂。参与者和评估结果的人员对治疗方案不知情。主要结局分别为每次接种后7天和28天内主动报告和自发报告的不良事件（AE）。次要结局为免疫原性指标（抗S IgG和假型病毒中和）。一项中期分析评估了治疗暴露个体在第57天的安全性以及按方案至第43天的免疫原性。ClinicalTrials.gov（NCT04764422）。
2021年3月20日至4月23日期间，377人接受筛查，210人入组（每组35人）；所有人均接种了第一剂；5人未接种第二剂。疫苗接种者中最常见的主动报告AE，大多为轻度，包括注射部位疼痛（<63%）、疲劳（<35%）、头痛（<32%）和肌痛（<32%）。报告与疫苗相关AE的比例在疫苗组中为5.7%至17.1%，在对照组中为2.9%；未出现与疫苗相关的严重不良事件。10 μg制剂的免疫原性最佳，其次是3 μg+CpG1018、3 μg、1 μg+CpG1018和1 μg制剂。在第43天，50%中和抗体的几何平均浓度范围为122.23 IU/mL（1 μg，95%CI 86.40 - 172.91）至474.35 IU/mL（10 μg，95%CI 320.90 - 701.19），93.9%至100%的疫苗组较基线水平升高≥4倍。
NDV-HXP-S具有可接受的安全性和较强的免疫原性。3 μg和3 μg+CpG1018制剂进入2期试验。
泰国国家疫苗研究所、泰国国家研究委员会、比尔及梅琳达·盖茨基金会、美国国立卫生研究院。
