PMID- 34580673
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220427
DP  - 2021 Sep 22
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 1/2 Trial.
LID - 2021.09.17.21263758 [pii]
LID - 10.1101/2021.09.17.21263758 [doi]
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 Newcastle disease virus vaccine expressing the spike protein of severe 
      acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It's being developed 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 adults aged 18-59 years, non-pregnant and 
      negative for SARS-CoV-2 antibodies were eligible. Participants were block 
      randomised to receive one of six treatments by intramuscular injection twice, 28 
      days apart: 1 microg+/-CpG1018 (a toll-like receptor 9 agonist), 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 enrolled (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 IU/mL (1 microg, 95% 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).
FAU - Pitisuttithum, Punnee
AU  - Pitisuttithum P
FAU - Luvira, Viravarn
AU  - Luvira V
FAU - Lawpoolsri, Saranath
AU  - Lawpoolsri S
FAU - Muangnoicharoen, Sant
AU  - Muangnoicharoen S
FAU - Kamolratanakul, Supitcha
AU  - Kamolratanakul S
FAU - Sivakorn, Chaisith
AU  - Sivakorn C
FAU - Narakorn, Piengthong
AU  - Narakorn P
FAU - Surichan, Somchaiya
AU  - Surichan S
FAU - Prangpratanporn, Sumalee
AU  - Prangpratanporn S
FAU - Puksuriwong, Suttida
AU  - Puksuriwong S
FAU - Lamola, Steven
AU  - Lamola S
FAU - Mercer, Laina D
AU  - Mercer LD
FAU - Raghunandan, Rama
AU  - Raghunandan R
FAU - Sun, Weina
AU  - Sun W
FAU - Liu, Yonghong
AU  - Liu Y
FAU - Carreno, Juan Manuel
AU  - Carreno JM
FAU - Scharf, Rami
AU  - Scharf R
FAU - Phumratanaprapin, Weerapong
AU  - Phumratanaprapin W
FAU - Amanat, Fatima
AU  - Amanat F
FAU - Gagnon, Luc
AU  - Gagnon L
FAU - Hsieh, Ching-Lin
AU  - Hsieh CL
FAU - Kaweepornpoj, Ruangchai
AU  - Kaweepornpoj R
FAU - Khan, Sarwat
AU  - Khan S
FAU - Lal, Manjari
AU  - Lal M
FAU - McCroskery, Stephen
AU  - McCroskery S
FAU - McLellan, Jason
AU  - McLellan J
FAU - Mena, Ignacio
AU  - Mena I
FAU - Meseck, Marcia
AU  - Meseck M
FAU - Phonrat, Benjaluck
AU  - Phonrat B
FAU - Sabmee, Yupa
AU  - Sabmee Y
FAU - Singchareon, Ratsamikorn
AU  - Singchareon R
FAU - Slamanig, Stefan
AU  - Slamanig S
FAU - Suthepakul, Nava
AU  - Suthepakul N
FAU - Tcheou, Johnstone
AU  - Tcheou J
FAU - Thantamnu, Narumon
AU  - Thantamnu N
FAU - Theerasurakarn, Sompone
AU  - Theerasurakarn S
FAU - Tran, Steven
AU  - Tran S
FAU - Vilasmongkolchai, Thanakrit
AU  - Vilasmongkolchai T
FAU - White, Jessica A
AU  - White JA
FAU - Garcia-Sastre, Adolfo
AU  - Garcia-Sastre A
FAU - Palese, Peter
AU  - Palese P
FAU - Krammer, Florian
AU  - Krammer F
FAU - Poopipatpol, Kittisak
AU  - Poopipatpol K
FAU - Wirachwong, Ponthip
AU  - Wirachwong P
FAU - Hjorth, Richard
AU  - Hjorth R
FAU - Innis, Bruce L
AU  - Innis BL
LA  - eng
SI  - ClinicalTrials.gov/NCT04764422
PT  - Preprint
DEP - 20210922
PL  - United States
TA  - medRxiv
JT  - medRxiv : the preprint server for health sciences
JID - 101767986
UIN - EClinicalMedicine. 2022 Mar 08;45:101323. PMID: 35284808
PMC - PMC8475960
EDAT- 2021/09/29 06:00
MHDA- 2021/09/29 06:01
PMCR- 2021/09/27
CRDT- 2021/09/28 06:43
PHST- 2021/09/28 06:43 [entrez]
PHST- 2021/09/29 06:00 [pubmed]
PHST- 2021/09/29 06:01 [medline]
PHST- 2021/09/27 00:00 [pmc-release]
AID - 2021.09.17.21263758 [pii]
AID - 10.1101/2021.09.17.21263758 [doi]
PST - epublish
SO  - medRxiv [Preprint]. 2021 Sep 22:2021.09.17.21263758. doi: 
      10.1101/2021.09.17.21263758.