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Safety, tolerability, and immunogenicity of an inactivated SARS-CoV-2 vaccine (CoronaVac) in healthy adults aged 60 years and older: a randomised, double-blind, placebo-controlled, phase 1/2 clinical trial.
Lancet Infect Dis. 2021 06; 21(6):803-812.LI

Abstract

BACKGROUND

A vaccine against COVID-19 is urgently needed for older adults, in whom morbidity and mortality due to the disease are increased. We aimed to assess the safety, tolerability, and immunogenicity of a candidate COVID-19 vaccine, CoronaVac, containing inactivated SARS-CoV-2, in adults aged 60 years and older.

METHODS

We did a randomised, double-blind, placebo-controlled, phase 1/2 clinical trial of CoronaVac in healthy adults aged 60 years and older in Renqiu (Hebei, China). Vaccine or placebo was given by intramuscular injection in two doses (days 0 and 28). Phase 1 comprised a dose-escalation study, in which participants were allocated to two blocks: block 1 (3 μg inactivated virus in 0·5 mL of aluminium hydroxide solution per injection) and block 2 (6 μg per injection). Within each block, participants were randomly assigned (2:1) using block randomisation to receive CoronaVac or placebo (aluminium hydroxide solution only). In phase 2, participants were randomly assigned (2:2:2:1) using block randomisation to receive either CoronaVac at 1·5 μg, 3 μg, or 6 μg per dose, or placebo. All participants, investigators, and laboratory staff were masked to treatment allocation. The primary safety endpoint was adverse reactions within 28 days after each injection in all participants who received at least one dose. The primary immunogenicity endpoint was seroconversion rate at 28 days after the second injection (which was assessed in all participants who had received the two doses of vaccine according to their random assignment, had antibody results available, and did not violate the trial protocol). Seroconversion was defined as a change from seronegative at baseline to seropositive for neutralising antibodies to live SARS-CoV-2 (positive cutoff titre 1/8), or a four-fold titre increase if the participant was seropositive at baseline. This study is ongoing and is registered with ClinicalTrials.gov (NCT04383574).

FINDINGS

Between May 22 and June 1, 2020, 72 participants (24 in each intervention group and 24 in the placebo group; mean age 65·8 years [SD 4·8]) were enrolled in phase 1, and between June 12 and June 15, 2020, 350 participants were enrolled in phase 2 (100 in each intervention group and 50 in the placebo group; mean age 66·6 years [SD 4·7] in 349 participants). In the safety populations from both phases, any adverse reaction within 28 days after injection occurred in 20 (20%) of 100 participants in the 1·5 μg group, 25 (20%) of 125 in the 3 μg group, 27 (22%) of 123 in the 6 μg group, and 15 (21%) of 73 in the placebo group. All adverse reactions were mild or moderate in severity and injection site pain (39 [9%] of 421 participants) was the most frequently reported event. As of Aug 28, 2020, eight serious adverse events, considered unrelated to vaccination, have been reported by seven (2%) participants. In phase 1, seroconversion after the second dose was observed in 24 of 24 participants (100·0% [95% CI 85·8-100·0]) in the 3 μg group and 22 of 23 (95·7% [78·1-99·9]) in the 6 μg group. In phase 2, seroconversion was seen in 88 of 97 participants in the 1·5 μg group (90·7% [83·1-95·7]), 96 of 98 in the 3 μg group (98·0% [92·8-99·8]), and 97 of 98 (99·0% [94·5-100·0]) in the 6 μg group. There were no detectable antibody responses in the placebo groups.

INTERPRETATION

CoronaVac is safe and well tolerated in older adults. Neutralising antibody titres induced by the 3 μg dose were similar to those of the 6 μg dose, and higher than those of the 1·5 μg dose, supporting the use of the 3 μg dose CoronaVac in phase 3 trials to assess protection against COVID-19.

FUNDING

Chinese National Key Research and Development Program and Beijing Science and Technology Program.

Authors+Show Affiliations

Hebei Provincial Center for Disease Control and Prevention, Shijiazhuang, Hebei, China.Sinovac Biotech, Beijing, China.National Institutes for Food and Drug Control, Beijing, China.National Institutes for Food and Drug Control, Beijing, China.Sinovac Biotech, Beijing, China.Beijing Key Tech Statistics Technology, Beijing, China.Hebei Provincial Center for Disease Control and Prevention, Shijiazhuang, Hebei, China.Renqiu City Center for Disease Control and Prevention, Renqiu, Hebei, China.Sinovac Life Sciences, Beijing, China.Renqiu City Center for Disease Control and Prevention, Renqiu, Hebei, China.Sinovac Biotech, Beijing, China.Beijing Key Tech Statistics Technology, Beijing, China.Renqiu City Center for Disease Control and Prevention, Renqiu, Hebei, China.Hebei Provincial Center for Disease Control and Prevention, Shijiazhuang, Hebei, China. Electronic address: yuliang_zh1@163.com.Sinovac Biotech, Beijing, China. Electronic address: yinwd@sinovac.com.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

33548194

Citation

Wu, Zhiwei, et al. "Safety, Tolerability, and Immunogenicity of an Inactivated SARS-CoV-2 Vaccine (CoronaVac) in Healthy Adults Aged 60 Years and Older: a Randomised, Double-blind, Placebo-controlled, Phase 1/2 Clinical Trial." The Lancet. Infectious Diseases, vol. 21, no. 6, 2021, pp. 803-812.
Wu Z, Hu Y, Xu M, et al. Safety, tolerability, and immunogenicity of an inactivated SARS-CoV-2 vaccine (CoronaVac) in healthy adults aged 60 years and older: a randomised, double-blind, placebo-controlled, phase 1/2 clinical trial. Lancet Infect Dis. 2021;21(6):803-812.
Wu, Z., Hu, Y., Xu, M., Chen, Z., Yang, W., Jiang, Z., Li, M., Jin, H., Cui, G., Chen, P., Wang, L., Zhao, G., Ding, Y., Zhao, Y., & Yin, W. (2021). Safety, tolerability, and immunogenicity of an inactivated SARS-CoV-2 vaccine (CoronaVac) in healthy adults aged 60 years and older: a randomised, double-blind, placebo-controlled, phase 1/2 clinical trial. The Lancet. Infectious Diseases, 21(6), 803-812. https://doi.org/10.1016/S1473-3099(20)30987-7
Wu Z, et al. Safety, Tolerability, and Immunogenicity of an Inactivated SARS-CoV-2 Vaccine (CoronaVac) in Healthy Adults Aged 60 Years and Older: a Randomised, Double-blind, Placebo-controlled, Phase 1/2 Clinical Trial. Lancet Infect Dis. 2021;21(6):803-812. PubMed PMID: 33548194.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Safety, tolerability, and immunogenicity of an inactivated SARS-CoV-2 vaccine (CoronaVac) in healthy adults aged 60 years and older: a randomised, double-blind, placebo-controlled, phase 1/2 clinical trial. AU - Wu,Zhiwei, AU - Hu,Yaling, AU - Xu,Miao, AU - Chen,Zhen, AU - Yang,Wanqi, AU - Jiang,Zhiwei, AU - Li,Minjie, AU - Jin,Hui, AU - Cui,Guoliang, AU - Chen,Panpan, AU - Wang,Lei, AU - Zhao,Guoqing, AU - Ding,Yuzhu, AU - Zhao,Yuliang, AU - Yin,Weidong, Y1 - 2021/02/03/ PY - 2020/11/18/received PY - 2020/12/07/revised PY - 2020/12/15/accepted PY - 2021/2/7/pubmed PY - 2021/2/7/medline PY - 2021/2/6/entrez SP - 803 EP - 812 JF - The Lancet. Infectious diseases JO - Lancet Infect Dis VL - 21 IS - 6 N2 - BACKGROUND: A vaccine against COVID-19 is urgently needed for older adults, in whom morbidity and mortality due to the disease are increased. We aimed to assess the safety, tolerability, and immunogenicity of a candidate COVID-19 vaccine, CoronaVac, containing inactivated SARS-CoV-2, in adults aged 60 years and older. METHODS: We did a randomised, double-blind, placebo-controlled, phase 1/2 clinical trial of CoronaVac in healthy adults aged 60 years and older in Renqiu (Hebei, China). Vaccine or placebo was given by intramuscular injection in two doses (days 0 and 28). Phase 1 comprised a dose-escalation study, in which participants were allocated to two blocks: block 1 (3 μg inactivated virus in 0·5 mL of aluminium hydroxide solution per injection) and block 2 (6 μg per injection). Within each block, participants were randomly assigned (2:1) using block randomisation to receive CoronaVac or placebo (aluminium hydroxide solution only). In phase 2, participants were randomly assigned (2:2:2:1) using block randomisation to receive either CoronaVac at 1·5 μg, 3 μg, or 6 μg per dose, or placebo. All participants, investigators, and laboratory staff were masked to treatment allocation. The primary safety endpoint was adverse reactions within 28 days after each injection in all participants who received at least one dose. The primary immunogenicity endpoint was seroconversion rate at 28 days after the second injection (which was assessed in all participants who had received the two doses of vaccine according to their random assignment, had antibody results available, and did not violate the trial protocol). Seroconversion was defined as a change from seronegative at baseline to seropositive for neutralising antibodies to live SARS-CoV-2 (positive cutoff titre 1/8), or a four-fold titre increase if the participant was seropositive at baseline. This study is ongoing and is registered with ClinicalTrials.gov (NCT04383574). FINDINGS: Between May 22 and June 1, 2020, 72 participants (24 in each intervention group and 24 in the placebo group; mean age 65·8 years [SD 4·8]) were enrolled in phase 1, and between June 12 and June 15, 2020, 350 participants were enrolled in phase 2 (100 in each intervention group and 50 in the placebo group; mean age 66·6 years [SD 4·7] in 349 participants). In the safety populations from both phases, any adverse reaction within 28 days after injection occurred in 20 (20%) of 100 participants in the 1·5 μg group, 25 (20%) of 125 in the 3 μg group, 27 (22%) of 123 in the 6 μg group, and 15 (21%) of 73 in the placebo group. All adverse reactions were mild or moderate in severity and injection site pain (39 [9%] of 421 participants) was the most frequently reported event. As of Aug 28, 2020, eight serious adverse events, considered unrelated to vaccination, have been reported by seven (2%) participants. In phase 1, seroconversion after the second dose was observed in 24 of 24 participants (100·0% [95% CI 85·8-100·0]) in the 3 μg group and 22 of 23 (95·7% [78·1-99·9]) in the 6 μg group. In phase 2, seroconversion was seen in 88 of 97 participants in the 1·5 μg group (90·7% [83·1-95·7]), 96 of 98 in the 3 μg group (98·0% [92·8-99·8]), and 97 of 98 (99·0% [94·5-100·0]) in the 6 μg group. There were no detectable antibody responses in the placebo groups. INTERPRETATION: CoronaVac is safe and well tolerated in older adults. Neutralising antibody titres induced by the 3 μg dose were similar to those of the 6 μg dose, and higher than those of the 1·5 μg dose, supporting the use of the 3 μg dose CoronaVac in phase 3 trials to assess protection against COVID-19. FUNDING: Chinese National Key Research and Development Program and Beijing Science and Technology Program. SN - 1474-4457 UR - https://www.unboundmedicine.com/medline/citation/33548194/Safety_tolerability_and_immunogenicity_of_an_inactivated_SARS_CoV_2_vaccine__CoronaVac__in_healthy_adults_aged_60_years_and_older:_a_randomised_double_blind_placebo_controlled_phase_1/2_clinical_trial_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1473-3099(20)30987-7 DB - PRIME DP - Unbound Medicine ER -
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