PMID- 35284808 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20230701 IS - 2589-5370 (Electronic) IS - 2589-5370 (Linking) VI - 45 DP - 2022 Mar TI - Safety and immunogenicity of an inactivated recombinant Newcastle disease virus vaccine expressing SARS-CoV-2 spike: Interim results of a randomised, placebo-controlled, phase 1 trial. PG - 101323 LID - 10.1016/j.eclinm.2022.101323 [doi] LID - 101323 AB - 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). CI - (c) 2022 The Author(s). FAU - Pitisuttithum, Punnee AU - Pitisuttithum P AD - Faculty of Tropical Medicine, Mahidol University, 420/6 Ratchawithi Road, Ratchathewi, Bangkok 10400, Thailand. FAU - Luvira, Viravarn AU - Luvira V AD - Faculty of Tropical Medicine, Mahidol University, 420/6 Ratchawithi Road, Ratchathewi, Bangkok 10400, Thailand. FAU - Lawpoolsri, Saranath AU - Lawpoolsri S AD - Faculty of Tropical Medicine, Mahidol University, 420/6 Ratchawithi Road, Ratchathewi, Bangkok 10400, Thailand. FAU - Muangnoicharoen, Sant AU - Muangnoicharoen S AD - Faculty of Tropical Medicine, Mahidol University, 420/6 Ratchawithi Road, Ratchathewi, Bangkok 10400, Thailand. FAU - Kamolratanakul, Supitcha AU - Kamolratanakul S AD - Faculty of Tropical Medicine, Mahidol University, 420/6 Ratchawithi Road, Ratchathewi, Bangkok 10400, Thailand. FAU - Sivakorn, Chaisith AU - Sivakorn C AD - Faculty of Tropical Medicine, Mahidol University, 420/6 Ratchawithi Road, Ratchathewi, Bangkok 10400, Thailand. FAU - Narakorn, Piengthong AU - Narakorn P AD - The Government Pharmaceutical Organization, 75/1 Rama VI Road, Ratchathewi, Bangkok 10400, Thailand. FAU - Surichan, Somchaiya AU - Surichan S AD - The Government Pharmaceutical Organization, 75/1 Rama VI Road, Ratchathewi, Bangkok 10400, Thailand. FAU - Prangpratanporn, Sumalee AU - Prangpratanporn S AD - The Government Pharmaceutical Organization, 75/1 Rama VI Road, Ratchathewi, Bangkok 10400, Thailand. FAU - Puksuriwong, Suttida AU - Puksuriwong S AD - The Government Pharmaceutical Organization, 75/1 Rama VI Road, Ratchathewi, Bangkok 10400, Thailand. FAU - Lamola, Steven AU - Lamola S AD - PATH, 2201 Westlake Avenue, Suite 200, Seattle, WA 98121, USA. FAU - Mercer, Laina D AU - Mercer LD AD - PATH, 2201 Westlake Avenue, Suite 200, Seattle, WA 98121, USA. FAU - Raghunandan, Rama AU - Raghunandan R AD - PATH, 2201 Westlake Avenue, Suite 200, Seattle, WA 98121, USA. FAU - Sun, Weina AU - Sun W AD - Department of Microbiology, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Pl, New York, NY 10029, USA. FAU - Liu, Yonghong AU - Liu Y AD - Department of Microbiology, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Pl, New York, NY 10029, USA. FAU - Carreno, Juan Manuel AU - Carreno JM AD - Department of Microbiology, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Pl, New York, NY 10029, USA. FAU - Scharf, Rami AU - Scharf R AD - PATH, 2201 Westlake Avenue, Suite 200, Seattle, WA 98121, USA. FAU - Phumratanaprapin, Weerapong AU - Phumratanaprapin W AD - Faculty of Tropical Medicine, Mahidol University, 420/6 Ratchawithi Road, Ratchathewi, Bangkok 10400, Thailand. FAU - Amanat, Fatima AU - Amanat F AD - Department of Microbiology, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Pl, New York, NY 10029, USA. FAU - Gagnon, Luc AU - Gagnon L AD - Nexelis, 525 Bd Cartier O, Laval, QC H7V 3S8, Canada. FAU - Hsieh, Ching-Lin AU - Hsieh CL AD - College of Natural Sciences, The University of Texas at Austin, 120 Inner Campus Dr Stop G2500, Austin, TX 78712, USA. FAU - Kaweepornpoj, Ruangchai AU - Kaweepornpoj R AD - The Government Pharmaceutical Organization, 75/1 Rama VI Road, Ratchathewi, Bangkok 10400, Thailand. FAU - Khan, Sarwat AU - Khan S AD - Nexelis, 525 Bd Cartier O, Laval, QC H7V 3S8, Canada. FAU - Lal, Manjari AU - Lal M AD - PATH, 2201 Westlake Avenue, Suite 200, Seattle, WA 98121, USA. FAU - McCroskery, Stephen AU - McCroskery S AD - Department of Microbiology, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Pl, New York, NY 10029, USA. FAU - McLellan, Jason AU - McLellan J AD - College of Natural Sciences, The University of Texas at Austin, 120 Inner Campus Dr Stop G2500, Austin, TX 78712, USA. FAU - Mena, Ignacio AU - Mena I AD - Department of Microbiology, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Pl, New York, NY 10029, USA. AD - Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Pl, New York, NY 10029, USA. FAU - Meseck, Marcia AU - Meseck M AD - The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Pl, New York, NY 10029, USA. FAU - Phonrat, Benjaluck AU - Phonrat B AD - Faculty of Tropical Medicine, Mahidol University, 420/6 Ratchawithi Road, Ratchathewi, Bangkok 10400, Thailand. FAU - Sabmee, Yupa AU - Sabmee Y AD - Faculty of Tropical Medicine, Mahidol University, 420/6 Ratchawithi Road, Ratchathewi, Bangkok 10400, Thailand. FAU - Singchareon, Ratsamikorn AU - Singchareon R AD - The Government Pharmaceutical Organization, 75/1 Rama VI Road, Ratchathewi, Bangkok 10400, Thailand. FAU - Slamanig, Stefan AU - Slamanig S AD - Department of Microbiology, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Pl, New York, NY 10029, USA. FAU - Suthepakul, Nava AU - Suthepakul N AD - The Government Pharmaceutical Organization, 75/1 Rama VI Road, Ratchathewi, Bangkok 10400, Thailand. FAU - Tcheou, Johnstone AU - Tcheou J AD - Department of Microbiology, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Pl, New York, NY 10029, USA. FAU - Thantamnu, Narumon AU - Thantamnu N AD - Faculty of Tropical Medicine, Mahidol University, 420/6 Ratchawithi Road, Ratchathewi, Bangkok 10400, Thailand. FAU - Theerasurakarn, Sompone AU - Theerasurakarn S AD - The Government Pharmaceutical Organization, 75/1 Rama VI Road, Ratchathewi, Bangkok 10400, Thailand. FAU - Tran, Steven AU - Tran S AD - Nexelis, 525 Bd Cartier O, Laval, QC H7V 3S8, Canada. FAU - Vilasmongkolchai, Thanakrit AU - Vilasmongkolchai T AD - The Government Pharmaceutical Organization, 75/1 Rama VI Road, Ratchathewi, Bangkok 10400, Thailand. FAU - White, Jessica A AU - White JA AD - PATH, 2201 Westlake Avenue, Suite 200, Seattle, WA 98121, USA. FAU - Bhardwaj, Nina AU - Bhardwaj N AD - The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Pl, New York, NY 10029, USA. FAU - Garcia-Sastre, Adolfo AU - Garcia-Sastre A AD - Department of Microbiology, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Pl, New York, NY 10029, USA. AD - Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Pl, New York, NY 10029, USA. AD - The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Pl, New York, NY 10029, USA. AD - Department of Medicine, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Pl, New York, NY 10029, USA. FAU - Palese, Peter AU - Palese P AD - Department of Microbiology, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Pl, New York, NY 10029, USA. AD - Department of Medicine, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Pl, New York, NY 10029, USA. FAU - Krammer, Florian AU - Krammer F AD - Department of Microbiology, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Pl, New York, NY 10029, USA. AD - Department of Pathology, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Pl, New York, NY 10029, USA. FAU - Poopipatpol, Kittisak AU - Poopipatpol K AD - The Government Pharmaceutical Organization, 75/1 Rama VI Road, Ratchathewi, Bangkok 10400, Thailand. FAU - Wirachwong, Ponthip AU - Wirachwong P AD - The Government Pharmaceutical Organization, 75/1 Rama VI Road, Ratchathewi, Bangkok 10400, Thailand. FAU - Hjorth, Richard AU - Hjorth R AD - PATH, 2201 Westlake Avenue, Suite 200, Seattle, WA 98121, USA. FAU - Innis, Bruce L AU - Innis BL AD - PATH, 2201 Westlake Avenue, Suite 200, Seattle, WA 98121, USA. LA - eng SI - ClinicalTrials.gov/NCT04764422 GR - R01 AI145870/AI/NIAID NIH HHS/United States GR - P01 AI097092/AI/NIAID NIH HHS/United States GR - 75N93021C00014/AI/NIAID NIH HHS/United States GR - 75N93019C00051/AI/NIAID NIH HHS/United States GR - P30 CA196521/CA/NCI NIH HHS/United States GR - INV-021239/GATES/Bill & Melinda Gates Foundation/United States PT - Journal Article DEP - 20220308 PL - England TA - EClinicalMedicine JT - EClinicalMedicine JID - 101733727 UOF - medRxiv. 2021 Sep 22;:. PMID: 34580673 PMC - PMC8903824 COIS- PN, SSur, SPra, SPuk, RK, RSin, NS, SThe, TV, KP, and PW are salaried employees of the Government Pharmaceutical Organization (Thailand). RH is a paid consultant to PATH. WS reports royalty payments from Avimex. AGS reports financial support from the U.S. NIAID (Centers of Excellence for Influenza Research and Response 75N93021C00014, Collaborative Influenza Vaccine Innovation Centers contract 75N93019C00051). The AGS laboratory has received research support from Pfizer, Senhwa Biosciences, Kenall Manufacturing, Avimex, Johnson & Johnson, Dynavax, 7Hills Pharma, Pharmamar, ImmunityBio, Accurius, Nanocomposix, Hexamer, N-fold LLC, Model Medicines, and Merck. AGS has consulting agreements for the following companies involving cash and/or stock: Vivaldi Biosciences, Contrafect, 7Hills Pharma, Avimex, Vaxalto, Pagoda, Accurius, Esperovax, Farmak, Applied Biological Laboratories, Curelab Oncology, Curelab Veterinary, and Pfizer; he also has received royalties (Merck, Astrazeneca, BI Vetmedica, Avimex, Regeneron), payment for lectures (Seqirus, Pharmamar), and participates in scientific advisory boards for New York State on Covid-19 vaccines, Accurius, Vaxalto, and Pfizer PP reports financial support from the U.S. NIAID (Centers of Excellence for Influenza Research and Response 75N93021C00014, P01 AI097092-07, R01 AI145870-03, Collaborative Influenza Vaccine Innovation Centers contract 75N93019C00051), payments involving cash and/or stock from Avimex, Vaxalto, and Accurius, royalty payments from Astrazeneca, BI Vetmedica, and Avimex; he also reports participation on the following advisory boards: New York State advisory board on Covid-19 vaccines, Accurius, and Vaxalto. PP also reports philanthropic grants or contracts through Mount Sinai. FK reports financial support from the U.S. NIAID (Collaborative Influenza Vaccine Innovation Centers contract 75N93019C00051, centre of Excellence for Influenza Research and Surveillance contract HHSN272201400008C), the JPB Foundation and the Open Philanthropy Project (research grant 2020-215,611, 5384), Pfizer, and the U.S. NCI ( contract 75N91019D00024, task order 75N91020F00003); he also has received royalties (Avimex), consulting fees (Pfizer, Seqirus, Third Rock Ventures, and Avimex), and payment for academic lectures during the past two years. NB reports participation as an AACR board member and support from SITC for travel and meeting attendance. CLH and JSM report financial support from the Bill & Melinda Gates Foundation and the U.S. NIH. The vaccine administered in this study was developed by faculty members at the Icahn School of Medicine at Mount Sinai including WS, PP, AGS, and FK. Mount Sinai has filed patent applications relating to SARS-CoV-2 serological assays and the NDV-based SARS-CoV-2 vaccine; the institution and its faculty inventors could benefit financially. JSM and CLH are inventors on a patent application concerning the Hexapro stabilized SARS-CoV-2 spike protein that was filed by the University of Texas at Austin and has been licensed to multiple entities; the university and its faculty inventors could benefit financially. All other authors have nothing to declare. EDAT- 2022/03/15 06:00 MHDA- 2022/03/15 06:01 PMCR- 2022/03/08 CRDT- 2022/03/14 06:01 PHST- 2021/10/13 00:00 [received] PHST- 2022/01/24 00:00 [revised] PHST- 2022/02/11 00:00 [accepted] PHST- 2022/03/14 06:01 [entrez] PHST- 2022/03/15 06:00 [pubmed] PHST- 2022/03/15 06:01 [medline] PHST- 2022/03/08 00:00 [pmc-release] AID - S2589-5370(22)00053-0 [pii] AID - 101323 [pii] AID - 10.1016/j.eclinm.2022.101323 [doi] PST - epublish SO - EClinicalMedicine. 2022 Mar 8;45:101323. doi: 10.1016/j.eclinm.2022.101323. eCollection 2022 Mar.