PMID- 34310400
OWN - NLM
STAT- MEDLINE
DCOM- 20210824
LR  - 20221207
IS  - 2542-5641 (Electronic)
IS  - 0366-6999 (Print)
IS  - 0366-6999 (Linking)
VI  - 134
IP  - 16
DP  - 2021 Jul 22
TI  - Immunogenicity and safety of a recombinant fusion protein vaccine (V-01) against 
      coronavirus disease 2019 in healthy adults: a randomized, double-blind, 
      placebo-controlled, phase II trial.
PG  - 1967-1976
LID - 10.1097/CM9.0000000000001702 [doi]
AB  - BACKGROUND: Innovative coronavirus disease 2019 (COVID-19) vaccines, with 
      elevated global manufacturing capacity, enhanced safety and efficacy, simplified 
      dosing regimens, and distribution that is less cold chain-dependent, are still 
      global imperatives for tackling the ongoing pandemic. A previous phase I trial 
      indicated that the recombinant COVID-19 vaccine (V-01), which contains a fusion 
      protein (IFN-PADRE-RBD-Fc dimer) as its antigen, is safe and well tolerated, 
      capable of inducing rapid and robust immune responses, and warranted further 
      testing in additional clinical trials. Herein, we aimed to assess the 
      immunogenicity and safety of V-01, providing rationales of appropriate dose 
      regimen for further efficacy study. METHODS: A randomized, double-blind, 
      placebo-controlled phase II clinical trial was initiated at the Gaozhou Municipal 
      Centre for Disease Control and Prevention (Guangdong, China) in March 2021. Both 
      younger (n = 440; 18-59 years of age) and older (n = 440; >/=60 years of age) adult 
      participants in this trial were sequentially recruited into two distinct groups: 
      two-dose regimen group in which participants were randomized either to follow a 
      10 or 25 mug of V-01 or placebo given intramuscularly 21 days apart (allocation 
      ratio, 3:3:1, n = 120, 120, 40 for each regimen, respectively), or one-dose 
      regimen groups in which participants were randomized either to receive a single 
      injection of 50 mug of V-01 or placebo (allocation ratio, 3:1, n = 120, 40, 
      respectively). The primary immunogenicity endpoints were the geometric mean 
      titers of neutralizing antibodies against live severe acute respiratory syndrome 
      coronavirus 2, and specific binding antibodies to the receptor binding domain 
      (RBD). The primary safety endpoint evaluation was the frequencies and percentages 
      of overall adverse events (AEs) within 30 days after full immunization. RESULTS: 
      V-01 provoked substantial immune responses in the two-dose group, achieving 
      encouragingly high titers of neutralizing antibody and anti-RBD immunoglobulin, 
      which peaked at day 35 (161.9 [95% confidence interval [CI]: 133.3-196.7] and 
      149.3 [95%CI: 123.9-179.9] in 10 and 25 mug V-01 group of younger adults, 
      respectively; 111.6 [95%CI: 89.6-139.1] and 111.1 [95%CI: 89.2-138.4] in 10 and 
      25 mug V-01 group of older adults, respectively), and remained high at day 49 
      after a day-21 second dose; these levels significantly exceed those in 
      convalescent serum from symptomatic COVID-19 patients (53.6, 95%CI: 31.3-91.7). 
      Our preliminary data show that V-01 is safe and well tolerated, with 
      reactogenicity predominantly being absent or mild in severity and only one 
      vaccine-related grade 3 or worse AE being observed within 30 days. The older 
      adult participants demonstrated a more favorable safety profile compared with 
      those in the younger adult group: with AEs percentages of 19.2%, 25.8%, 17.5% in 
      older adults vs. 34.2%, 23.3%, 26.7% in younger adults at the 10, 25 mug V-01 
      two-dose group, and 50 mug V-01 one-dose group, respectively. CONCLUSIONS: The 
      vaccine candidate V-01 appears to be safe and immunogenic. The preliminary 
      findings support the advancement of the two-dose, 10 mug V-01 regimen to a phase 
      III trial for a large-scale population-based evaluation of safety and efficacy. 
      TRIAL REGISTRATION: http://www.chictr.org.cn/index.aspx (No. ChiCTR2100045107, 
      http://www.chictr.org.cn/showproj.aspx?proj=124702).
CI  - Copyright (c) 2021 The Chinese Medical Association, produced by Wolters Kluwer, 
      Inc. under the CC-BY-NC-ND license.
FAU - Shu, Ya-Jun
AU  - Shu YJ
AD  - Guangdong Provincial Institute of Biological Products and Materia Medica, 
      Guangzhou, Guangdong 510440, China.
FAU - He, Jian-Feng
AU  - He JF
AD  - Guangdong Provincial Center for Disease Control and Prevention, Guangzhou, 
      Guangdong 511430, China.
FAU - Pei, Rong-Juan
AU  - Pei RJ
AD  - Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, Hubei 430071, 
      China.
FAU - He, Peng
AU  - He P
AD  - National Institutes for Food and Drug Control, Beijing 100050, China.
FAU - Huang, Zhu-Hang
AU  - Huang ZH
AD  - Guangdong Provincial Institute of Biological Products and Materia Medica, 
      Guangzhou, Guangdong 510440, China.
FAU - Chen, Shao-Min
AU  - Chen SM
AD  - Guangdong Provincial Institute of Biological Products and Materia Medica, 
      Guangzhou, Guangdong 510440, China.
FAU - Ou, Zhi-Qiang
AU  - Ou ZQ
AD  - Guangdong Provincial Institute of Biological Products and Materia Medica, 
      Guangzhou, Guangdong 510440, China.
FAU - Deng, Jing-Long
AU  - Deng JL
AD  - Gaozhou Center for Disease Control and Prevention, Maoming, Guangdong 525000, 
      China.
FAU - Zeng, Pei-Yu
AU  - Zeng PY
AD  - Gaozhou Center for Disease Control and Prevention, Maoming, Guangdong 525000, 
      China.
FAU - Zhou, Jian
AU  - Zhou J
AD  - Gaozhou Center for Disease Control and Prevention, Maoming, Guangdong 525000, 
      China.
FAU - Min, Yuan-Qin
AU  - Min YQ
AD  - Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, Hubei 430071, 
      China.
FAU - Deng, Fei
AU  - Deng F
AD  - Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, Hubei 430071, 
      China.
FAU - Peng, Hua
AU  - Peng H
AD  - Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese 
      Academy of Sciences, Beijing 100101, China.
FAU - Zhang, Zheng
AU  - Zhang Z
AD  - Institute for Hepatology, National Clinical Research Center for Infectious 
      Disease, Shenzhen Third People's Hospital, Shenzhen, Guangdong 518112, China.
FAU - Wang, Bo
AU  - Wang B
AD  - Livzon Bio Inc., Zhuhai, Guangdong 519045, China.
FAU - Xu, Zhong-Hui
AU  - Xu ZH
AD  - Livzon Bio Inc., Zhuhai, Guangdong 519045, China.
FAU - Guan, Wu-Xiang
AU  - Guan WX
AD  - Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, Hubei 430071, 
      China.
FAU - Hu, Zhong-Yu
AU  - Hu ZY
AD  - National Institutes for Food and Drug Control, Beijing 100050, China.
FAU - Zhang, Ji-Kai
AU  - Zhang JK
AD  - Guangdong Provincial Institute of Biological Products and Materia Medica, 
      Guangzhou, Guangdong 510440, China.
LA  - eng
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Randomized Controlled Trial
DEP - 20210722
PL  - China
TA  - Chin Med J (Engl)
JT  - Chinese medical journal
JID - 7513795
RN  - 0 (Antibodies, Viral)
RN  - 0 (COVID-19 Vaccines)
RN  - 0 (Recombinant Fusion Proteins)
SB  - IM
MH  - Aged
MH  - Antibodies, Viral
MH  - *COVID-19/therapy
MH  - COVID-19 Vaccines
MH  - Double-Blind Method
MH  - Humans
MH  - Immunization, Passive
MH  - Recombinant Fusion Proteins
MH  - SARS-CoV-2
MH  - COVID-19 Serotherapy
PMC - PMC8382383
COIS- Bo Wang and Zhong-Hui Xu are the employees of Livzon Bio Inc., China. All other 
      authors declare no competing interests.
EDAT- 2021/07/27 06:00
MHDA- 2021/08/25 06:00
PMCR- 2021/08/20
CRDT- 2021/07/26 17:22
PHST- 2021/07/27 06:00 [pubmed]
PHST- 2021/08/25 06:00 [medline]
PHST- 2021/07/26 17:22 [entrez]
PHST- 2021/08/20 00:00 [pmc-release]
AID - 00029330-202108200-00011 [pii]
AID - CMJ-2021-1972 [pii]
AID - 10.1097/CM9.0000000000001702 [doi]
PST - epublish
SO  - Chin Med J (Engl). 2021 Jul 22;134(16):1967-1976. doi: 
      10.1097/CM9.0000000000001702.