Thursday, March 26, 2015

New Ebola Vaccine Found Safe In Early Human Trials

New Ebola Vaccine Found Safe In Early Human Trials

Introduction:

Since its first outbreak occurred in 1976, Zaire Ebola virus have been associated with 14 outbreaks reported up to 2014. Ebola viruses are enveloped, non-segmented, negative-strand RNA viruses belonging to the family of Filoviridae. Five different species of Ebola virus have been identified: Zaire, Sudan, C├┤te d'Ivoire, Reston, and Bundibugyo. The Zaire Ebola virus in 2014 causing the most serious outbreak was considered to be a new epidemic strain, with GP homology of the gene was only 97.6%, compared to the GP gene of the strain in 1976.

Five different species of Ebola virus have been identified

Researchers have developed an investigational Ad5-EBOV vaccine was developed according to the 2014 epidemic Zaire strain and formulated as freeze-dry products which could be stored at 4℃.

Result show that the high-dose vaccine is safe and robustly immunogenic

Methodology:

Researchers carried a randomised, double-blind, placebo-controlled, phase 1 clinical trial at one site in Taizhou County, Jiangsu Province, China. Healthy adults (aged 18–60 years) were sequentially enrolled and randomly assigned (2:1), by computer-generated block randomisation (block size of six), to receive placebo, low-dose adenovirus type-5 vector-based Ebola vaccine, or high-dose vaccine. Randomisation was pre-stratified by dose group. All participants, investigators, and laboratory staff were masked to treatment allocation. The primary safety endpoint was occurrence of solicited adverse reactions within 7 days of vaccination. The primary immunogenicity endpoints were glycoprotein-specific antibody titres and T-cell responses at day 28 after the vaccination. Analysis was by intention to treat. The study is registered with ClinicalTrials.gov, number NCT02326194.

Results:

Result show that the high-dose vaccine is safe and robustly immunogenic. One shot of the high-dose vaccine could mount glycoprotein-specific humoral and T-cell response against Ebola virus in 14 days. 

The adenovirus type-5 Ebola virus has a good safety profile in healthy adults. The incidence of adverse reactions was in line with findings from previous studies of other viral-vectored Ebola vaccines. A significantly higher incidence of pain at the injection site was noted in participants in the high-dose vaccine group, probably because of a high dose of viral particles. But almost all the reported adverse reactions or events were mild or moderate, and the high-dose vaccine was still well tolerated.

The magnitude of the immune response to the vaccine was dose-dependent. Ebola glycoprotein-specific antibody was significantly increased by day 14, and continued to increase up to day 28 after the vaccination, whereas the Ebola glycoprotein-specific T-cell responses peaked at day 14. 

However, both vaccine-elicited Ebola glycoprotein-specific antibody response and T-cell response were partly blunted by the presence of pre-existing anti-adenovirus type-5 immunity, especially in participants in the low-dose group. 

The high-dose vaccine could overcome the negative effects of pre-existing immunity and still induced robust Ebola glycoprotein-specific antibody and T-cell responses in participants with a high baseline concentration of neutralising antibody. Because a large proportion of adults have pre-existing adenovirus type-5 immunity, especially in developing countries, a high dose of the viral particles would seem necessary.

Article citation: Chen, W.; et. al. Safety and immunogenicity of a novel recombinant adenovirus type-5 vector-based Ebola vaccine in healthy adults in China: preliminary report of a randomised, double-blind, placebo-controlled, phase 1 trial. Lancet 2015DOI: http://dx.doi.org/10.1016/S0140-6736(15)60553-0