Este artigo é um Preprint
Preprints são relatos preliminares de pesquisa que não foram certificados pela revisão por pares. Eles não devem ser considerados para orientar a prática clínica ou comportamentos relacionados à saúde e não devem ser publicados na mídia como informação estabelecida.
Preprints publicados online permitem que os autores recebam feedback rápido, e toda a comunidade científica pode avaliar o trabalho independentemente e responder adequadamente. Estes comentários são publicados juntamente com os preprints para qualquer pessoa ler e servir como uma avaliação pós-publicação.
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
Preprint
em Inglês
| medRxiv
| ID: ppmedrxiv-22270253
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 g +/-CpG1018 (a toll-like receptor 9 agonist), 3 g alone, 10 g 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 g formulation group was highest, followed by 1 g +CpG1018, 3 g, and 1 g 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 g, 95% CI 37.01, 84.94) to 246.19 IU/mL (10 g, 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 g +/-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 g dose was advanced to phase 2 along with a 6 g dose. The 10 g dose was not selected for evaluation in phase 2 due to potential impact on manufacturing capacity. ClinicalTrials.gov NCT04830800.
cc_by_nd
Texto completo:
Disponível
Coleções:
Preprints
Base de dados:
medRxiv
Tipo de estudo:
Experimental_studies
/
Estudo observacional
/
Estudo prognóstico
/
Rct
Idioma:
Inglês
Ano de publicação:
2022
Tipo de documento:
Preprint