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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.
Chin Med J (Engl). 2021 07 22; 134(16):1967-1976.CM

Abstract

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 μg 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 μg 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 μg 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 μg 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 μg V-01 two-dose group, and 50 μg 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 μg 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).

Authors+Show Affiliations

Guangdong Provincial Institute of Biological Products and Materia Medica, Guangzhou, Guangdong 510440, China.Guangdong Provincial Center for Disease Control and Prevention, Guangzhou, Guangdong 511430, China.Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, Hubei 430071, China.National Institutes for Food and Drug Control, Beijing 100050, China.Guangdong Provincial Institute of Biological Products and Materia Medica, Guangzhou, Guangdong 510440, China.Guangdong Provincial Institute of Biological Products and Materia Medica, Guangzhou, Guangdong 510440, China.Guangdong Provincial Institute of Biological Products and Materia Medica, Guangzhou, Guangdong 510440, China.Gaozhou Center for Disease Control and Prevention, Maoming, Guangdong 525000, China.Gaozhou Center for Disease Control and Prevention, Maoming, Guangdong 525000, China.Gaozhou Center for Disease Control and Prevention, Maoming, Guangdong 525000, China.Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, Hubei 430071, China.Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, Hubei 430071, China.Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.Institute for Hepatology, National Clinical Research Center for Infectious Disease, Shenzhen Third People's Hospital, Shenzhen, Guangdong 518112, China.Livzon Bio Inc., Zhuhai, Guangdong 519045, China.Livzon Bio Inc., Zhuhai, Guangdong 519045, China.Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, Hubei 430071, China.National Institutes for Food and Drug Control, Beijing 100050, China.Guangdong Provincial Institute of Biological Products and Materia Medica, Guangzhou, Guangdong 510440, China.

Pub Type(s)

Clinical Trial, Phase II
Journal Article
Randomized Controlled Trial

Language

eng

PubMed ID

34310400

Citation

Shu, Ya-Jun, et al. "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." Chinese Medical Journal, vol. 134, no. 16, 2021, pp. 1967-1976.
Shu YJ, He JF, Pei RJ, et al. 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. Chin Med J (Engl). 2021;134(16):1967-1976.
Shu, Y. J., He, J. F., Pei, R. J., He, P., Huang, Z. H., Chen, S. M., Ou, Z. Q., Deng, J. L., Zeng, P. Y., Zhou, J., Min, Y. Q., Deng, F., Peng, H., Zhang, Z., Wang, B., Xu, Z. H., Guan, W. X., Hu, Z. Y., & Zhang, J. K. (2021). 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. Chinese Medical Journal, 134(16), 1967-1976. https://doi.org/10.1097/CM9.0000000000001702
Shu YJ, et al. 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. Chin Med J (Engl). 2021 07 22;134(16):1967-1976. PubMed PMID: 34310400.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Shu,Ya-Jun, AU - He,Jian-Feng, AU - Pei,Rong-Juan, AU - He,Peng, AU - Huang,Zhu-Hang, AU - Chen,Shao-Min, AU - Ou,Zhi-Qiang, AU - Deng,Jing-Long, AU - Zeng,Pei-Yu, AU - Zhou,Jian, AU - Min,Yuan-Qin, AU - Deng,Fei, AU - Peng,Hua, AU - Zhang,Zheng, AU - Wang,Bo, AU - Xu,Zhong-Hui, AU - Guan,Wu-Xiang, AU - Hu,Zhong-Yu, AU - Zhang,Ji-Kai, Y1 - 2021/07/22/ PY - 2021/7/27/pubmed PY - 2021/8/25/medline PY - 2021/7/26/entrez SP - 1967 EP - 1976 JF - Chinese medical journal JO - Chin Med J (Engl) VL - 134 IS - 16 N2 - 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 μg 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 μg 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 μg 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 μg 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 μg V-01 two-dose group, and 50 μg 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 μg 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). SN - 2542-5641 UR - https://www.unboundmedicine.com/medline/citation/34310400/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_ L2 - https://doi.org/10.1097/CM9.0000000000001702 DB - PRIME DP - Unbound Medicine ER -