Modified vaccinia Ankara booster increases immunogenic response in Ebola Virus disease

1. Chimpanzee adenovirus 3 (ChAd3) vaccination boosted with modified vaccinia Ankara (MVA) elicited superior B- and T-cell immune responses to the Zaire ebolavirus than those induced by the ChAd3 vaccine alone.

2. The safety profile for MVA was found to be acceptable.

Evidence Rating Level: 2 (Good)

Study Rundown: Ebola virus disease (EVD) is a deadly infection with a high case fatality rate. In light of 2014’s West African Ebola outbreak, development and testing of an Ebola vaccine has been a priority. There has been some promising phase 1 and phase 3 vaccine results however these vaccines have a relatively short duration of action and are likely most helpful in limiting the spread of infection among close contacts of those with EVD. However, in earlier stages of an outbreak where transmission is unpredictable and new cases appear in geographically distinct locations, a vaccine of longer duration would be necessary. This phase 1 investigated the effect of adding a booster dose of MVA to the ChAd3 vaccine on the amount and duration of B-cell and T-cell immune responses as compared to ChAd3 vaccine.

The study results demonstrated that the ChAd3 vaccine that was boosted with MVA elicited higher levels and longer duration of virus-specific and neutralizing antibodies as compared to ChAd3 vaccination alone. The virus-specific antibody response remained positive 6 months after vaccination regardless of MVA booster status, however, those who received MVA boosters had a significantly higher titre levels.

Click to read the study in NEJM

Relevant Reading: Evaluation of Convalescent Plasma for Ebola Virus Disease in Guinea

In-Depth [randomized controlled trial]: This phase 1 study was conducted at the Centre for Clinical Vaccinology and Tropical Medicine at the University of Oxford in the United Kingdom. Participants included healthy adults from 18 to 50. The 60 participants were administered the ChAd3 vaccine: 20 received a lower dose of 1×10¹⁰ viral particles, 20 received a dose of 2.5×10¹⁰ viral particles and 20 received the vaccine in a dose of 5×10¹⁰ viral particles. Ten participants from each dosage group were then given a single booster dose of MVA. These 30 individuals received another booster MVA dose 3 to 10 weeks following the priming immunization. Antibody responses were analyzed using 4 different IgG ELISAs. Separate T-cell assays (ELISPOT) were used to measure the T-cell response.

There were no safety concerns across all ChAd3 dosing regimens. Use of the MVA boosting routine resulted in a 12x increase in virus-specific antibodies (geometric mean titer, 9007) and a 5x increase in CD8+ T-cells. There were also significant increases in the titers of neutralizing antibodies (geometric mean titer, 139; p<0.001). These virus-specific antibodies remained positive in the participants’ blood for a 6-month duration, however those who received the MVA booster had significantly higher levels than those who did not.

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