1. 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
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Anh Duc Dang, Thiem Dinh Vu, Ha Hai Vu, Van Thanh Ta, Anh Thi Van Pham, Mai Thi Ngoc Dang, Be Van Le, Thai Huu Duong, Duoc Van Nguyen, Saranath Lawpoolsri, Pailinrut Chinwangso, Jason S. McLellan, Ching-Lin Hsieh, Adolfo Garcia-Sastre, Peter Palese, Weina Sun, Jose L. Martinez, Irene Gonzalez-Dominguez, Stefan Slamanig, Juan Manuel Carreño, Johnstone Tcheou, Florian Krammer, Ariel Raskin, Huong Minh Vu, Thang Cong Tran, Huong Mai Nguyen, Laina D. Mercer, Rama Raghunandan, Manjari Lal, Jessica A. White, Richard Hjorth, Bruce L. Innis, and Rami Scharf
- Subjects
Adult ,COVID-19 Vaccines ,Adolescent ,General Veterinary ,General Immunology and Microbiology ,SARS-CoV-2 ,Immunization, Passive ,Newcastle disease virus ,Public Health, Environmental and Occupational Health ,COVID-19 ,Middle Aged ,Antibodies, Viral ,Antibodies, Neutralizing ,Young Adult ,Immunogenicity, Vaccine ,Infectious Diseases ,Adjuvants, Immunologic ,Double-Blind Method ,Vaccines, Inactivated ,Vietnam ,Spike Glycoprotein, Coronavirus ,Humans ,Molecular Medicine ,COVID-19 Serotherapy - Abstract
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 μg +/-CpG1018 (a toll-like receptor 9 agonist), 3 μg alone, 10 μg 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 (ClinicalTrials.govNCT04830800.
- Published
- 2022
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