Lihua Wu1,2, Zhe Zhang3, Hainv Gao2,4, Yuhua Li5, Lihua Hou3, Hangping Yao1,2, Shipo Wu3, Jian Liu1,2, Ling Wang5, You Zhai1,2, Huilin Ou1,2, Meihua Lin1,2, Xiaoxin Wu2,4, Jingjing Liu5, Guanjing Lang1,2, Qian Xin6, Guolan Wu1,2, Li Luo7, Pei Liu7, Jianzhong Shentu1,2, Nanping Wu1,2, Jifang Sheng1,2, Yunqing Qiu1,2, Wei Chen3, Lanjuan Li1,2,4. 1. a The First Affiliated Hospital, College of Medicine, Zhejiang University , Xiacheng District, Hangzhou , Zhejiang , China. 2. b The Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases , Xiacheng District, Hangzhou , Zhejiang , China. 3. c Beijing Institute of Biotechnology , Haidian District, Beijing , China. 4. d Zhejiang University International Hospital , Xiacheng District, Hangzhou , Zhejiang , China. 5. e National Institutes for Food and Drug Control , Chongwen District, Beijing , China. 6. f The General Hospital of People's Liberation Army , Beijing , China. 7. g Department of Epidemiology and Biostatistics , School of Public Health, Southeast University , Nanjing , Jiangsu , China.
Abstract
BACKGROUND: To determine the safety and immunogenicity of a novel recombinant adenovirus type 5 vector based Ebola virus disease vaccine (Ad5-EBOV) in Africans in China. METHODS: A phase 1, dose-escalation, open-label trial was conducted. 61 healthy Africans were sequentially enrolled, with 31 participants receiving one shot intramuscular injection and 30 participants receiving a double-shot regimen. Primary and secondary end points related to safety and immunogenicity were assessed within 28 d after vaccination. This study was registered with ClinicalTrials.gov (NCT02401373). RESULTS: Ad5-EBOV is well tolerated and no adverse reaction of grade 3 or above was observed. 53 (86.89%) participants reported at least one adverse reaction within 28 d of vaccination. The most common reaction was fever and the mild pain at injection site, and there were no significant difference between these 2 groups. Ebola glycoprotein-specific antibodies appeared in all 61 participants and antibodies titers peaked after 28 d of vaccination. The geometric mean titres (GMTs) were similar between these 2 groups (1919.01 vs 1684.70 P = 0.5562). The glycoprotein-specific T-cell responses rapidly peaked after 14 d of vaccination and then decreased, however, the percentage of subjects with responses were much higher in the high-dose group (60.00% vs 9.68%, P = 0.0014). Pre-existing Ad5 neutralizing antibodies could significantly dampen the specific humoral immune response and cellular response to the vaccine. CONCLUSION: The application of Ad5-EBOV demonstrated safe in Africans in China and a specific GP antibody and T-cell response could occur 14 d after the first immunization. This acceptable safety profile provides a reliable basis to proceed with trials in Africa.
BACKGROUND: To determine the safety and immunogenicity of a novel recombinant adenovirus type 5 vector based Ebola virus disease vaccine (Ad5-EBOV) in Africans in China. METHODS: A phase 1, dose-escalation, open-label trial was conducted. 61 healthy Africans were sequentially enrolled, with 31 participants receiving one shot intramuscular injection and 30 participants receiving a double-shot regimen. Primary and secondary end points related to safety and immunogenicity were assessed within 28 d after vaccination. This study was registered with ClinicalTrials.gov (NCT02401373). RESULTS: Ad5-EBOV is well tolerated and no adverse reaction of grade 3 or above was observed. 53 (86.89%) participants reported at least one adverse reaction within 28 d of vaccination. The most common reaction was fever and the mild pain at injection site, and there were no significant difference between these 2 groups. Ebola glycoprotein-specific antibodies appeared in all 61 participants and antibodies titers peaked after 28 d of vaccination. The geometric mean titres (GMTs) were similar between these 2 groups (1919.01 vs 1684.70 P = 0.5562). The glycoprotein-specific T-cell responses rapidly peaked after 14 d of vaccination and then decreased, however, the percentage of subjects with responses were much higher in the high-dose group (60.00% vs 9.68%, P = 0.0014). Pre-existing Ad5 neutralizing antibodies could significantly dampen the specific humoral immune response and cellular response to the vaccine. CONCLUSION: The application of Ad5-EBOV demonstrated safe in Africans in China and a specific GP antibody and T-cell response could occur 14 d after the first immunization. This acceptable safety profile provides a reliable basis to proceed with trials in Africa.
Entities:
Keywords:
Ad5-EBOV; GP antibody; T-cell response; immunogenicity; safety
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