| アブストラクト | BACKGROUND: 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 recombinant Newcastle disease virus vaccine expressing the spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It's being developed by public sector manufacturers in Thailand, Vietnam, and Brazil; herein are initial results from Thailand. METHODS: 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 males and non-pregnant females, aged 18-59 years and negative for SARS-CoV-2 antibodies, were eligible. Participants were randomised to receive one of six treatments by intramuscular injection twice, 28 days apart: 1 microg, 1 microg+CpG1018 (a toll-like receptor 9 agonist), 3 microg, 3 microg+CpG1018, 10 microg, 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). FINDINGS: Between March 20 and April 23, 2021, 377 individuals were screened and 210 were enroled (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 microg formulation's immunogenicity ranked best, followed by 3 microg+CpG1018, 3 microg, 1 microg+CpG1018, and 1 microg formulations. On day 43, the geometric mean concentrations of 50% neutralising antibody ranged from 122.23 international units per mL (IU/mL; 1 microg, 95% confidence interval (CI) 86.40-172.91) to 474.35 IU/mL (10 microg, 95% CI 320.90-701.19), with 93.9% to 100% of vaccine groups attaining a >/= 4-fold increase over baseline. INTERPRETATION: NDV-HXP-S had an acceptable safety profile and potent immunogenicity. The 3 microg and 3 microg+CpG1018 formulations advanced to phase 2. FUNDING: National Vaccine Institute (Thailand), National Research Council (Thailand), Bill & Melinda Gates Foundation, National Institutes of Health (USA). |
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| ジャーナル名 | EClinicalMedicine |
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| 投稿日 | 2022/3/15 |
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| 投稿者 | 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; Carreno, 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; Bhardwaj, Nina; Garcia-Sastre, Adolfo; Palese, Peter; Krammer, Florian; Poopipatpol, Kittisak; Wirachwong, Ponthip; Hjorth, Richard; Innis, Bruce L |
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| 組織名 | Faculty of Tropical Medicine, Mahidol University, 420/6 Ratchawithi Road,;Ratchathewi, Bangkok 10400, Thailand.;The Government Pharmaceutical Organization, 75/1 Rama VI Road, Ratchathewi,;Bangkok 10400, Thailand.;PATH, 2201 Westlake Avenue, Suite 200, Seattle, WA 98121, USA.;Department of Microbiology, Icahn School of Medicine at Mount Sinai, 1 Gustave L.;Levy Pl, New York, NY 10029, USA.;Nexelis, 525 Bd Cartier O, Laval, QC H7V 3S8, Canada.;College of Natural Sciences, The University of Texas at Austin, 120 Inner Campus;Dr Stop G2500, Austin, TX 78712, USA.;Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount;Sinai, 1 Gustave L. Levy Pl, New York, NY 10029, USA.;The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, 1 Gustave L.;Department of Medicine, Icahn School of Medicine at Mount Sinai, 1 Gustave L.;Department of Pathology, Icahn School of Medicine at Mount Sinai, 1 Gustave L. |
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| Pubmed リンク | https://www.ncbi.nlm.nih.gov/pubmed/35284808/ |
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