PMID- 35577631 OWN - NLM STAT- MEDLINE DCOM- 20220603 LR - 20240211 IS - 1873-2518 (Electronic) IS - 0264-410X (Print) IS - 0264-410X (Linking) VI - 40 IP - 26 DP - 2022 Jun 9 TI - Safety and immunogenicity of an egg-based inactivated Newcastle disease virus vaccine expressing SARS-CoV-2 spike: Interim results of a randomized, placebo-controlled, phase 1/2 trial in Vietnam. PG - 3621-3632 LID - S0264-410X(22)00526-6 [pii] LID - 10.1016/j.vaccine.2022.04.078 [doi] AB - 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 (NDV) vaccine expressing the spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Wuhan-Hu-1. The spike protein was stabilized and incorporated into NDV virions by removing the polybasic furin cleavage site, introducing the transmembrane domain and cytoplasmic tail of the fusion protein of NDV, and introducing six prolines for stabilization in the prefusion state. Vaccine production and clinical development was initiated in Vietnam, Thailand, and Brazil. Here the interim results from the first stage of the randomized, dose-escalation, observer-blind, placebo-controlled, phase 1/2 trial conducted at the Hanoi Medical University (Vietnam) are presented. Healthy adults aged 18-59 years, non-pregnant, and with self-reported negative history for SARS-CoV-2 infection were eligible. Participants were randomized to receive one of five treatments by intramuscular injection twice, 28 days apart: 1 mug +/- CpG1018 (a toll-like receptor 9 agonist), 3 mug alone, 10 mug alone, or placebo. Participants and personnel assessing outcomes were masked to treatment. The primary outcomes were solicited adverse events (AEs) during 7 days and subject-reported AEs during 28 days after each vaccination. Investigators further reviewed subject-reported AEs. Secondary outcomes were immunogenicity measures (anti-spike immunoglobulin G [IgG] and pseudotyped virus neutralization). This interim analysis assessed safety 56 days after first vaccination (day 57) in treatment-exposed individuals and immunogenicity through 14 days after second vaccination (day 43) per protocol. Between March 15 and April 23, 2021, 224 individuals were screened and 120 were enrolled (25 per group for active vaccination and 20 for placebo). All subjects received two doses. The most common solicited AEs among those receiving active vaccine or placebo were all predominantly mild and included injection site pain or tenderness (<58%), fatigue or malaise (<22%), headache (<21%), and myalgia (<14%). No higher proportion of the solicited AEs were observed for any group of active vaccine. The proportion reporting vaccine-related AEs during the 28 days after either vaccination ranged from 4% to 8% among vaccine groups and was 5% in controls. No vaccine-related serious adverse event occurred. The immune response in the 10 mug formulation group was highest, followed by 1 mug + CpG1018, 3 mug, and 1 mug formulations. Fourteen days after the second vaccination, the geometric mean concentrations (GMC) of 50% neutralizing antibody against the homologous Wuhan-Hu-1 pseudovirus ranged from 56.07 IU/mL (1 mug, 95% CI 37.01, 84.94) to 246.19 IU/mL (10 mug, 95% CI 151.97, 398.82), with 84% to 96% of vaccine groups attaining a >/= 4-fold increase over baseline. This was compared to a panel of human convalescent sera (N = 29, 72.93 95% CI 33.00-161.14). Live virus neutralization to the B.1.617.2 (Delta) variant of concern was reduced but in line with observations for vaccines currently in use. Since the adjuvant has shown modest benefit, GMC ratio of 2.56 (95% CI, 1.4-4.6) for 1 mug +/- CpG1018, a decision was made not to continue studying it with this vaccine. NDV-HXP-S had an acceptable safety profile and potent immunogenicity. The 3 mug dose was advanced to phase 2 along with a 6 mug dose. The 10 mug dose was not selected for evaluation in phase 2 due to potential impact on manufacturing capacity. ClinicalTrials.gov NCT04830800. CI - Copyright (c) 2022 The Authors. Published by Elsevier Ltd.. All rights reserved. FAU - Duc Dang, Anh AU - Duc Dang A AD - National Institute of Hygiene and Epidemiology, 1 Yersin Street, Hai Ba Trung District, Hanoi, Viet Nam. FAU - Dinh Vu, Thiem AU - Dinh Vu T AD - National Institute of Hygiene and Epidemiology, 1 Yersin Street, Hai Ba Trung District, Hanoi, Viet Nam. FAU - Hai Vu, Ha AU - Hai Vu H AD - National Institute of Hygiene and Epidemiology, 1 Yersin Street, Hai Ba Trung District, Hanoi, Viet Nam. FAU - Thanh Ta, Van AU - Thanh Ta V AD - Hanoi Medical University, 1 Ton That Tung Street, Dong Da District, Hanoi, Viet Nam. FAU - Thi Van Pham, Anh AU - Thi Van Pham A AD - Hanoi Medical University, 1 Ton That Tung Street, Dong Da District, Hanoi, Viet Nam. FAU - Thi Ngoc Dang, Mai AU - Thi Ngoc Dang M AD - Hanoi Medical University, 1 Ton That Tung Street, Dong Da District, Hanoi, Viet Nam. FAU - Van Le, Be AU - Van Le B AD - Institute of Vaccines and Medical Biologicals, 9 Pasteur, Xuong Huan, Nha Trang City, Khanh Hoa, Viet Nam. FAU - Huu Duong, Thai AU - Huu Duong T AD - Institute of Vaccines and Medical Biologicals, 9 Pasteur, Xuong Huan, Nha Trang City, Khanh Hoa, Viet Nam. FAU - Van Nguyen, Duoc AU - Van Nguyen D AD - Institute of Vaccines and Medical Biologicals, 9 Pasteur, Xuong Huan, Nha Trang City, Khanh Hoa, Viet Nam. FAU - Lawpoolsri, Saranath AU - Lawpoolsri S AD - Center of Excellence for Biomedical and Public Health Informatics (BIOPHICS), Faculty of Tropical Medicine, Mahidol University, 420/6 Ratchawithi Road, Ratchathewi, Bangkok 10400, Thailand; Department of Tropical Hygiene, Faculty of Tropical Medicine, Mahidol University, 420/6 Ratchawithi Road, Ratchathewi, Bangkok 10400, Thailand. FAU - Chinwangso, Pailinrut AU - Chinwangso P AD - Center of Excellence for Biomedical and Public Health Informatics (BIOPHICS), Faculty of Tropical Medicine, Mahidol University, 420/6 Ratchawithi Road, Ratchathewi, Bangkok 10400, Thailand. FAU - McLellan, Jason S AU - McLellan JS AD - College of Natural Sciences, The University of Texas at Austin, 120 Inner Campus Dr Stop G2500, Austin, TX 78712, USA. 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 - 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; Department of Pathology, Molecular and Cell Based Medicine Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Pl, New York, NY 10029, USA; The Global Health and Emerging Pathogen Institute, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Pl, New York, NY 10029, USA; Department of Medicine, 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. 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; Department of Medicine, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Pl, New York, NY 10029, 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 - Martinez, Jose L AU - Martinez JL AD - Department of Microbiology, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Pl, New York, NY 10029, USA. FAU - Gonzalez-Dominguez, Irene AU - Gonzalez-Dominguez I AD - Department of Microbiology, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Pl, New York, NY 10029, USA. 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 - Manuel Carreno, Juan AU - Manuel Carreno J AD - Department of Microbiology, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Pl, New York, NY 10029, USA. 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 - 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; Department of Pathology, Molecular and Cell Based Medicine Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Pl, New York, NY 10029, USA. FAU - Raskin, Ariel AU - Raskin A AD - Department of Microbiology, Icahn School of Medicine at Mount Sinai, 1 Gustave L. Levy Pl, New York, NY 10029, USA. FAU - Minh Vu, Huong AU - Minh Vu H AD - WHO Vietnam Country Office, 304 Kim Ma Street, Ba Dinh District, Hanoi, Viet Nam. FAU - Cong Tran, Thang AU - Cong Tran T AD - PATH Vietnam, 1101, 11th Floor, Hanoi Towers, 49 Hai Ba Trung Street, Hoan Kiem District, Hanoi, Viet Nam. FAU - Mai Nguyen, Huong AU - Mai Nguyen H AD - PATH Vietnam, 1101, 11th Floor, Hanoi Towers, 49 Hai Ba Trung Street, Hoan Kiem District, Hanoi, Viet Nam. 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 - Lal, Manjari AU - Lal M AD - PATH, 2201 Westlake Avenue, Suite 200, Seattle, WA 98121, USA. FAU - White, Jessica A AU - White JA AD - PATH, 2201 Westlake Avenue, Suite 200, Seattle, WA 98121, USA. 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. Electronic address: binnis@path.org. FAU - Scharf, Rami AU - Scharf R AD - PATH, 2201 Westlake Avenue, Suite 200, Seattle, WA 98121, USA. Electronic address: rscharf@path.org. LA - eng SI - ClinicalTrials.gov/NCT04830800 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 - 001/WHO_/World Health Organization/International GR - INV-021239/GATES/Bill & Melinda Gates Foundation/United States PT - Clinical Trial, Phase I PT - Clinical Trial, Phase II PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20220514 PL - Netherlands TA - Vaccine JT - Vaccine JID - 8406899 RN - 0 (Adjuvants, Immunologic) RN - 0 (Antibodies, Neutralizing) RN - 0 (Antibodies, Viral) RN - 0 (COVID-19 Vaccines) RN - 0 (Spike Glycoprotein, Coronavirus) RN - 0 (Vaccines, Inactivated) RN - 0 (spike protein, SARS-CoV-2) RN - SARS-CoV-2 variants SB - IM MH - Adjuvants, Immunologic MH - Adolescent MH - Adult MH - Antibodies, Neutralizing MH - Antibodies, Viral MH - *COVID-19/prevention & control/therapy MH - COVID-19 Vaccines/adverse effects MH - Double-Blind Method MH - Humans MH - Immunization, Passive MH - Immunogenicity, Vaccine MH - Middle Aged MH - Newcastle disease virus/genetics MH - *SARS-CoV-2 MH - Spike Glycoprotein, Coronavirus MH - Vaccines, Inactivated/adverse effects MH - Vietnam MH - Young Adult MH - COVID-19 Serotherapy PMC - PMC9106407 OTO - NOTNLM OT - COVID-19 OT - Egg-based vaccine OT - Newcastle disease virus OT - SARS-CoV-2 COIS- Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2022/05/17 06:00 MHDA- 2022/06/07 06:00 PMCR- 2022/06/09 CRDT- 2022/05/16 22:04 PHST- 2022/02/03 00:00 [received] PHST- 2022/04/03 00:00 [revised] PHST- 2022/04/25 00:00 [accepted] PHST- 2022/05/17 06:00 [pubmed] PHST- 2022/06/07 06:00 [medline] PHST- 2022/05/16 22:04 [entrez] PHST- 2022/06/09 00:00 [pmc-release] AID - S0264-410X(22)00526-6 [pii] AID - 10.1016/j.vaccine.2022.04.078 [doi] PST - ppublish SO - Vaccine. 2022 Jun 9;40(26):3621-3632. doi: 10.1016/j.vaccine.2022.04.078. Epub 2022 May 14.