Open-label phase I clinical trial of Ad5-EBOV in Africans in China

• Main Authors: Lihua Wu (Author), Zhe Zhang (Author), Hainv Gao (Author), Yuhua Li (Author), Lihua Hou (Author), Hangping Yao (Author), Shipo Wu (Author), Jian Liu (Author), Ling Wang (Author), You Zhai (Author), Huilin Ou (Author), Meihua Lin (Author), Xiaoxin Wu (Author), Jingjing Liu (Author), Guanjing Lang (Author), Qian Xin (Author), Guolan Wu (Author), Li Luo (Author), Pei Liu (Author), Jianzhong Shentu (Author), Nanping Wu (Author), Jifang Sheng (Author), Yunqing Qiu (Author), Wei Chen (Author), Lanjuan Li (Author)
• Format: Book
• Published: Taylor & Francis Group, 2017-09-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.
• Notes: 2164-5515; 2164-554X; 10.1080/21645515.2017.1342021
• Keywords: ad5-ebov; gp antibody; immunogenicity; safety; t-cell response; Immunologic diseases. Allergy; RC581-607; Therapeutics. Pharmacology; RM1-950
• Source: Human Vaccines & Immunotherapeutics, Vol 13, Iss 9, Pp 2078-2085 (2017)

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.