Ebola and Marburg vaccines safe and well tolerated in Phase 1b trial in Uganda

1. The Ebola and Marburg vaccines were shown to be safe and well tolerated when given as part of a series of three injections both as separate and combined vaccinations, with no serious adverse events reported.

2. The Ebola and Marburg vaccines generated virus antigen-specific humoral and cellular immune responses when given both as separate and combined vaccinations.

Evidence Rating Level: 1 (Excellent)      

Study Rundown: The Ebola and Marburg viruses belong to a group of highly contagious and fatal infectious diseases known as Filoviridae, causing viral hemorrhagic fever. Ebola virus in particular has garnered widespread attention due to the latest 2014 outbreak, which has had globally reaching effects with a case fatality rate of almost 40%. Researchers have attempted to develop vaccines capable of curbing these diseases before they can spread any further worldwide. This study was a phase 1b trial in Uganda that assessed the safety profiles and immunogenicity for two new recombinant DNA vaccines against the Sudan and Zaire strains of the Ebola (EBO) virus and Marburg (MAR) virus both separately and together.

The results showed that both the EBO and MAR vaccines given separately and together were safe and tolerable. Both vaccines also generated Ebola or Marburg virus antigen-specific humoral and cellular immune responses. Strengths of this study include that it assessed the efficacy of both vaccines separately and together, which is imperative for areas such as Africa where Ebola and Marburg are both endemic. Limitations to this study were that the immunogenicity rates did not surpass 63% in any of the vaccine groups, which is concerning because these vaccines may not generate a sufficient immune response in the future if used for acute outbreaks. As such, future work is necessary to improve the immunogenicity of these vaccines.

This study was funded by the US Department of Defense Infectious Disease Clinical Research Program and US National Institutes of Health Intramural Research Program

Click to read the study in The Lancet

Relevant Reading: Chimpanzee Adenovirus Vector Ebola Vaccine — Preliminary Report

In-Depth [randomized controlled trial]: This study included 108 healthy individuals aged 18-50 during November 2009 – April 2010 in Uganda. Participants were randomly assigned (5:1) to receive vaccine or placebo and allocated into one of four groups: EBO vaccine only (n=30), MAR vaccine only (n=30), EBO and MAR vaccine together (n=30), or placebo (n=18). Individuals were given a series of three intramuscular injections at least 21 days apart at 0, 21-35, and 49-63 days. The primary objective of the study assessed the safety and tolerability of the vaccines given separately and together as measured by local and systemic reactivity and adverse events. The secondary objectives assessed the immunogenicity of the vaccines four weeks after the third injection, as measured by humoral and cellular immunity responses using ELISA assays and ELISpot, respectively.

100 (93%) of 108 total participants completed all three injections. Both vaccines were well tolerated, with most participants reporting only mild local tenderness or pain. There were no significant differences between systemic or local adverse reactions between groups. Four participants had adverse events leading to vaccine termination, including partial thromboplastin time prolongation, syncope, and unexplained lower leg swelling. Neutropenia was the most common adverse event reported, although the authors concluded that it was unrelated to the vaccinations. Both vaccines generated humoral and cellular immune responses, with no significant differences between single and combined vaccinations. 57% of the EBO vaccine group generated positive titers to the EBO Sudan glycoprotein (95% CI 37-75), as compared with 47% of those receiving both vaccines (95% CI, 28-66), while 50% of the EBO vaccine group generated positive titers to the EBO Zaire glycoprotein (95% CI 31-69), as well as 50% of those receiving both vaccines (95% CI 31-69). Additionally, 31% in the MAR vaccine group generated positive titers to the Marburg glycoprotein (95% CI 15-51), compared with 23% of those receiving both vaccines (95% CI 10-42). Results were similar for cellular immunity analyses for both vaccines.

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Image: PD/CDC

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