Final trial results confirm Ebola vaccine provides high protection against disease - WHO - Could be available in 2018

[Gert van der Hoek]

Safety and immunogenicity of a recombinant adenovirus type-5 vector-based Ebola vaccine in healthy adults in Sierra Leone: a single-centre, randomised, double-blind, placebo-controlled, phase 2 trial


[FONT=&quot]Published: [/FONT][FONT=&quot]22 December 2016[/FONT]

Summary

Background

[FONT=&quot]A recombinant adenovirus type-5 vector-based vaccine expressing the glycoprotein of Ebola Zaire Makona variant showed good safety and immunogenicity in a phase 1 trial of healthy Chinese adults. We aimed to assess the safety and immunogenicity of this vaccine in healthy adults in Sierra Leone and to determine the optimal dose.[/FONT]

Methods

[FONT=&quot]We did a single-centre, randomised, double-blind, placebo-controlled, phase 2 clinical trial at Sierra Leone–China Friendship Hospital, Freetown, Sierra Leone. We recruited healthy adults aged 18–50 years who were HIV negative, had no history of Ebola virus infection, and had no previous immunisation with other Ebola vaccine candidates. Participants were sequentially enrolled and randomly assigned (2:1:1), by computer-generated block randomisation (block size of eight), to receive the high-dose vaccine (1?6 ? 1011 viral particles), low-dose vaccine (8?0 ? 1010 viral particles), or placebo (containing only vaccine excipients, with no viral particles). Participants, investigators, and study staff (except two study pharmacists) were masked from treatment allocation. The primary safety outcome was occurrence of solicited adverse reactions within 7 days of vaccination, analysed by intention to treat. The primary immunogenicity outcome was glycoprotein-specific antibody responses at days 14, 28, and 168 after vaccination, analysed in all vaccinated participants who had blood samples drawn for antibody tests. The trial is registered with the Pan African Clinical Trials Registry, number PACTR201509001259869, and is completed.[/FONT]

Findings

[FONT=&quot]During Oct 10–28, 2015, 500 participants were enrolled and randomly assigned to receive the high-dose vaccine (n=250), low-dose vaccine (n=125), or placebo (n=125). 132 (53%) participants in the high-dose group, 60 (48%) in the low-dose group, and 54 (43%) in the placebo group reported at least one solicited adverse reaction within 7 days of vaccination. Most adverse reactions were mild and self-limiting. Solicited injection-site adverse reactions were significantly more frequent in vaccine recipients (65 [26%] in high-dose group and 31 [25%] in low-dose group) than in those receiving placebo (17 [14%]; p=0?0169). Glycoprotein-specific antibody responses were detected from day 14 onwards (geometric mean titre 1251?0 [95% CI 976?6–1602?5] in low-dose group and 1728?4 [1459?4–2047?0] in high-dose group) and peaked at day 28 (1471?8 [1151?0–1881?8] and 2043?1 [1762?4–2368?4]), but declined quickly in the following months (223?3 [148?2–336?4] and 254?2 [185?0–349?5] at day 168). Geometric mean titres in the placebo group remained around 6?0–6?8 throughout the study period. Three serious adverse events (malaria, gastroenteritis, and one fatal asthma episode) were reported in the high-dose vaccine group, but none was deemed related to the vaccine.[/FONT]

Interpretation

[FONT=&quot]The recombinant adenovirus type-5 vector-based Ebola vaccine was safe and highly immunogenic in healthy Sierra Leonean adults, and 8?0 ? 1010 viral particles was the optimal dose.[/FONT]

Funding

[FONT=&quot]Chinese Ministry of Science and Technology and the National Health and Family Planning Commission, Beijing Institute of Biotechnology, and Tianjin CanSino Biotechnology.[/FONT]

 

[Gert van der Hoek]

Final trial results confirm Ebola vaccine provides high protection against disease

News release

23 DECEMBER 2016 | GENEVA - An experimental Ebola vaccine was highly protective against the deadly virus in a major trial in Guinea, according to results published today in The Lancet. The vaccine is the first to prevent infection from one of the most lethal known pathogens, and the findings add weight to early trial results published last year.

The vaccine, called rVSV-ZEBOV, was studied in a trial involving 11 841 people in Guinea during 2015. Among the 5837 people who received the vaccine, no Ebola cases were recorded 10 days or more after vaccination. In comparison, there were 23 cases 10 days or more after vaccination among those who did not receive the vaccine.

The trial was led by WHO, together with Guinea’s Ministry of Health, Medecins sans Frontieres and the Norwegian Institute of Public Health, in collaboration with other international partners.

"While these compelling results come too late for those who lost their lives during West Africa's Ebola epidemic, they show that when the next Ebola outbreak hits, we will not be defenceless," said Dr Marie-Paule Kieny, WHO’s Assistant Director-General for Health Systems and Innovation, and the study’s lead author.

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In January, GAVI, the Vaccine Alliance provided US$5 million to Merck towards the future procurement of the vaccine once it is approved, prequalified and recommended by WHO. As part of this agreement, Merck committed to ensure that 300 000 doses of the vaccine are available for emergency use in the interim, and to submit the vaccine for licensure by the end of 2017. Merck has also submitted the vaccine to WHO’s Emergency Use and Assessment Listing procedure, a mechanism through which experimental vaccines, medicines and diagnostics can be made available for use prior to formal licensure.

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