Tags

Type your tag names separated by a space and hit enter

Immunity duration of a recombinant adenovirus type-5 vector-based Ebola vaccine and a homologous prime-boost immunisation in healthy adults in China: final report of a randomised, double-blind, placebo-controlled, phase 1 trial.
Lancet Glob Health 2017; 5(3):e324-e334LG

Abstract

BACKGROUND

The 2013-15 Ebola virus disease epidemic in west Africa greatly accelerated the development of Ebola vaccine. We aimed to analyse the immune persistence induced by one shot of an adenovirus type-5 vector-based Ebola virus vaccine up to 6 months and the effect of boosting with a homologous vector in healthy adults in China.

METHODS

In a randomised, double-blind, placebo-controlled, phase 1 clinical trial in one site in Jiangsu Province, China, 120 healthy adults aged 18-60 years received an initial dose of intramuscular adenovirus type-5 Ebola virus vaccine of 4·0 × 1010 viral particles, 1·6 × 1011 viral particles, or placebo, and were followed up to day 168. Participants were subsequently re-recruited to receive a booster dose of the same vaccine or placebo, in the same dose, at month 6. Women who were pregnant, breastfeeding, or planned to become pregnant during the next month were excluded. Randomisation was conducted by computer-generated block randomisation. Randomisation data were unmasked for interim analysis of the data obtained between days 0-28 but not disclosed to participants or site staff. Safety and immunogenicity analysis were done on the intention-to-treat population. We aimed to assess the safety profile of the experimental vaccine and the immunity responses to a single-dose immunisation or a homologous prime-boost regimen. Primary outcomes were Ebola glycoprotein-specific ELISA antibody responses 28 days post-boost and the occurrences of adverse reactions post-boost. The original trial and the extended booster study were registered with ClinicalTrials.gov, numbers NCT02326194 and NCT02533791, respectively.

FINDINGS

Between Dec 28, 2014, and Jan 9, 2015, we enrolled 210 volunteers. 90 participants were not randomised due to not meeting inclusion criteria (61), meeting exclusion criteria (4), or withdrawal of consent (25). 120 people were randomly assigned to receive intramuscular Ebola vaccine at 4·0 × 1010 viral particles (low dose, n=40), Ebola vaccine at 1·6 × 1011 viral particles (high dose, n=40), or placebo (n=40, in two groups of 20). After prime vaccination, the geometric mean titer (GMT) of ELISA EC90 peaked at 682·7 (95% CI 424·3-1098·5) in the low-dose vaccine group and 1305·7 (970·1-1757·2) in the high-dose vaccine group at day 28, and then fell gradually through the next a few months to 575·5 (394·8-838·8) in the high-dose vaccine group and 197·9 (107·9-362·7) in the low-dose vaccine group at day 168. No specific response was recorded in the placebo group with a GMT of 5·0. Of the 120 participants involved in the initial trial, ten participants declined to participate, and 110 were included in the boost immunisation: 38 received the low dose, 35 received the high dose, and 37 received the placebo. At day 28 after boost vaccination, the ELISA EC90 titres rapidly rose to 6110 (95% CI 4705-7935) in the low-dose group and to 11825 (8904-15705) in the high dose group. 78 of 110 participants reported at least one solicited adverse reaction within the first 7 days after booster administration. Both of the groups who received vaccine showed significantly higher incidence of mild or moderate solicited adverse reactions than did the placebo group.

INTERPRETATION

The adenovirus 5-vectored Ebola vaccine of 1·6 × 1011 viral particles was highly immunogenic and safe. The lower dose of 4·0 × 1010 viral particles was also safe, but immunogenicity seemed to be more vulnerable to the pre-existing immunity of adenovirus 5. A homologous priming-boosting regimen with adenovirus type-5 Ebola vaccine at 6 months interval was able to elicit greater antibody responses with longer duration. These results support an immunisation strategy to implement a booster injection for a more durable protection against Ebola virus disease.

FUNDING

Chinese Ministry of Science and Technology and The National Health and Family Planning Commission, Beijing Institute of Biotechnology, and Tianjin CanSino Biotechnology.

Authors+Show Affiliations

Jiangsu Provincial Center for Disease Control and Prevention, Nanjing 210009, Jiangsu Province, China.Beijing Institute of Biotechnology, Fengtai District, Beijing 100039, China.Jiangsu Provincial Center for Disease Control and Prevention, Nanjing 210009, Jiangsu Province, China.Beijing Institute of Biotechnology, Fengtai District, Beijing 100039, China.Jiangsu Provincial Center for Disease Control and Prevention, Nanjing 210009, Jiangsu Province, China.Jiangsu Provincial Center for Disease Control and Prevention, Nanjing 210009, Jiangsu Province, China.Jiangsu Provincial Center for Disease Control and Prevention, Nanjing 210009, Jiangsu Province, China.Beijing Institute of Biotechnology, Fengtai District, Beijing 100039, China.Beijing Institute of Biotechnology, Fengtai District, Beijing 100039, China.Jiangsu Provincial Center for Disease Control and Prevention, Nanjing 210009, Jiangsu Province, China.Jiangsu Provincial Center for Disease Control and Prevention, Nanjing 210009, Jiangsu Province, China.School of Public Health, Southeast University, Nanjing 210009, Jiangsu Province, China.Jiangsu Provincial Center for Disease Control and Prevention, Nanjing 210009, Jiangsu Province, China.School of Public Health, Southeast University, Nanjing 210009, Jiangsu Province, China.Tianjin CanSino Biotechnology Inc, TEDA West District, Tianjin 300457, China.Jiangsu Provincial Center for Disease Control and Prevention, Nanjing 210009, Jiangsu Province, China. Electronic address: jszfc@vip.sina.com.Beijing Institute of Biotechnology, Fengtai District, Beijing 100039, China. Electronic address: cw0226@foxmail.com.

Pub Type(s)

Clinical Trial, Phase I
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

28017642

Citation

Li, Jing-Xin, et al. "Immunity Duration of a Recombinant Adenovirus Type-5 Vector-based Ebola Vaccine and a Homologous Prime-boost Immunisation in Healthy Adults in China: Final Report of a Randomised, Double-blind, Placebo-controlled, Phase 1 Trial." The Lancet. Global Health, vol. 5, no. 3, 2017, pp. e324-e334.
Li JX, Hou LH, Meng FY, et al. Immunity duration of a recombinant adenovirus type-5 vector-based Ebola vaccine and a homologous prime-boost immunisation in healthy adults in China: final report of a randomised, double-blind, placebo-controlled, phase 1 trial. Lancet Glob Health. 2017;5(3):e324-e334.
Li, J. X., Hou, L. H., Meng, F. Y., Wu, S. P., Hu, Y. M., Liang, Q., ... Chen, W. (2017). Immunity duration of a recombinant adenovirus type-5 vector-based Ebola vaccine and a homologous prime-boost immunisation in healthy adults in China: final report of a randomised, double-blind, placebo-controlled, phase 1 trial. The Lancet. Global Health, 5(3), pp. e324-e334. doi:10.1016/S2214-109X(16)30367-9.
Li JX, et al. Immunity Duration of a Recombinant Adenovirus Type-5 Vector-based Ebola Vaccine and a Homologous Prime-boost Immunisation in Healthy Adults in China: Final Report of a Randomised, Double-blind, Placebo-controlled, Phase 1 Trial. Lancet Glob Health. 2017;5(3):e324-e334. PubMed PMID: 28017642.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Immunity duration of a recombinant adenovirus type-5 vector-based Ebola vaccine and a homologous prime-boost immunisation in healthy adults in China: final report of a randomised, double-blind, placebo-controlled, phase 1 trial. AU - Li,Jing-Xin, AU - Hou,Li-Hua, AU - Meng,Fan-Yue, AU - Wu,Shi-Po, AU - Hu,Yue-Mei, AU - Liang,Qi, AU - Chu,Kai, AU - Zhang,Zhe, AU - Xu,Jun-Jie, AU - Tang,Rong, AU - Wang,Wen-Juan, AU - Liu,Pei, AU - Hu,Jia-Lei, AU - Luo,Li, AU - Jiang,Rong, AU - Zhu,Feng-Cai, AU - Chen,Wei, Y1 - 2016/12/23/ PY - 2016/10/19/received PY - 2016/11/24/revised PY - 2016/11/30/accepted PY - 2016/12/27/pubmed PY - 2017/12/27/medline PY - 2016/12/27/entrez SP - e324 EP - e334 JF - The Lancet. Global health JO - Lancet Glob Health VL - 5 IS - 3 N2 - BACKGROUND: The 2013-15 Ebola virus disease epidemic in west Africa greatly accelerated the development of Ebola vaccine. We aimed to analyse the immune persistence induced by one shot of an adenovirus type-5 vector-based Ebola virus vaccine up to 6 months and the effect of boosting with a homologous vector in healthy adults in China. METHODS: In a randomised, double-blind, placebo-controlled, phase 1 clinical trial in one site in Jiangsu Province, China, 120 healthy adults aged 18-60 years received an initial dose of intramuscular adenovirus type-5 Ebola virus vaccine of 4·0 × 1010 viral particles, 1·6 × 1011 viral particles, or placebo, and were followed up to day 168. Participants were subsequently re-recruited to receive a booster dose of the same vaccine or placebo, in the same dose, at month 6. Women who were pregnant, breastfeeding, or planned to become pregnant during the next month were excluded. Randomisation was conducted by computer-generated block randomisation. Randomisation data were unmasked for interim analysis of the data obtained between days 0-28 but not disclosed to participants or site staff. Safety and immunogenicity analysis were done on the intention-to-treat population. We aimed to assess the safety profile of the experimental vaccine and the immunity responses to a single-dose immunisation or a homologous prime-boost regimen. Primary outcomes were Ebola glycoprotein-specific ELISA antibody responses 28 days post-boost and the occurrences of adverse reactions post-boost. The original trial and the extended booster study were registered with ClinicalTrials.gov, numbers NCT02326194 and NCT02533791, respectively. FINDINGS: Between Dec 28, 2014, and Jan 9, 2015, we enrolled 210 volunteers. 90 participants were not randomised due to not meeting inclusion criteria (61), meeting exclusion criteria (4), or withdrawal of consent (25). 120 people were randomly assigned to receive intramuscular Ebola vaccine at 4·0 × 1010 viral particles (low dose, n=40), Ebola vaccine at 1·6 × 1011 viral particles (high dose, n=40), or placebo (n=40, in two groups of 20). After prime vaccination, the geometric mean titer (GMT) of ELISA EC90 peaked at 682·7 (95% CI 424·3-1098·5) in the low-dose vaccine group and 1305·7 (970·1-1757·2) in the high-dose vaccine group at day 28, and then fell gradually through the next a few months to 575·5 (394·8-838·8) in the high-dose vaccine group and 197·9 (107·9-362·7) in the low-dose vaccine group at day 168. No specific response was recorded in the placebo group with a GMT of 5·0. Of the 120 participants involved in the initial trial, ten participants declined to participate, and 110 were included in the boost immunisation: 38 received the low dose, 35 received the high dose, and 37 received the placebo. At day 28 after boost vaccination, the ELISA EC90 titres rapidly rose to 6110 (95% CI 4705-7935) in the low-dose group and to 11825 (8904-15705) in the high dose group. 78 of 110 participants reported at least one solicited adverse reaction within the first 7 days after booster administration. Both of the groups who received vaccine showed significantly higher incidence of mild or moderate solicited adverse reactions than did the placebo group. INTERPRETATION: The adenovirus 5-vectored Ebola vaccine of 1·6 × 1011 viral particles was highly immunogenic and safe. The lower dose of 4·0 × 1010 viral particles was also safe, but immunogenicity seemed to be more vulnerable to the pre-existing immunity of adenovirus 5. A homologous priming-boosting regimen with adenovirus type-5 Ebola vaccine at 6 months interval was able to elicit greater antibody responses with longer duration. These results support an immunisation strategy to implement a booster injection for a more durable protection against Ebola virus disease. FUNDING: Chinese Ministry of Science and Technology and The National Health and Family Planning Commission, Beijing Institute of Biotechnology, and Tianjin CanSino Biotechnology. SN - 2214-109X UR - https://www.unboundmedicine.com/medline/citation/28017642/Immunity_duration_of_a_recombinant_adenovirus_type_5_vector_based_Ebola_vaccine_and_a_homologous_prime_boost_immunisation_in_healthy_adults_in_China:_final_report_of_a_randomised_double_blind_placebo_controlled_phase_1_trial_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S2214-109X(16)30367-9 DB - PRIME DP - Unbound Medicine ER -