Are we Closer to Having an Ebola Vaccine?

Shanterra Grable, Mercer University College of Pharmacy

Ebola Virus Disease (EVD), also called Ebola hemorrhagic fever, was first discovered in 1976 in South Sudan and the Democratic Republic of Congo. The transmission of Ebola can be attributed to close contact with infected persons by healthcare workers and lack of infection control precautions. Traditional burial practices that involve direct contact with the deceased can also account for Ebola transmission. It is important to note that if not treated, someone with Ebola remains infectious as long as the virus is in the person’s blood. [1] Treatment of Ebola is nonspecific and involves supportive care, rehydration with fluids, and symptom management. [2]

In March 2014, west Africa had its largest Ebola virus outbreak, and multiple countries were also affected including the United States. Although it is currently under control, the Center for Disease Control continues to search for ways to further prevent the spread of the infection such as through vaccination. [2] There are no approved Ebola vaccines or treatments available. However, a phase 2 placebo-controlled trial conducted in the height of the most recent outbreak to evaluate the safety and immune response of two new Ebola vaccines. The results were recently published and summarized below. [3]  

Phase two placebo-controlled trial of two vaccines to prevent Ebola in Liberia
Design Randomized, placebo-controlled, phase 2 trial; N= 1,500
Objective To evaluate the safety and immunogenicity of the ChAd3-EBO-Z vaccine and the rVSV∆G-ZEBOV-GP vaccine compared to placebo
Study Groups
  • ChAd3-EBO-Z vaccine (n=500)
  • rVSV∆G-ZEBOV-GP vaccine (n=500)
  • Placebo (n=500)
Methods Participants were randomized to receive an intramuscular injection of 2 ml of ChAd3-EBO-Z vaccine, 2 ml of rVSV∆G-ZEBOV-GP vaccine, or 1 ml of saline placebo.

Inclusion criteria:  at least 18 years of age at time of enrollment

Exclusion criteria: history of EVD, temperature more than 38°C, women pregnant or breastfeeding

Duration February 2015 to April 2016
Primary Outcome Measure Positive vaccine response measured as log 10 titer of IgG antibodies against Ebola surface glycoprotein increased by a factor of four or more from baseline
Baseline Characteristics ChAd3-EBO-Z

(n=500)

rVSV∆G-ZEBOV-GP

(n=500)

Placebo

(n=500)

Age, years 30 29 30
Female (%) 37.0 37.4 35.4
Body mass index 21.4 22.0 21.7
Contact in past month with person who had Ebola virus disease (%) 0.2 1.0 1.0
Work involves possible contact with person with Ebola virus disease (%) 4.4 5.0 4.4
HIV positive (%) 5.0 4.4 6.2
Syphilis (%) 6.0 4.4 5.0
Ebola IgG titer (EU/ml) 75 81 79
Positive antibody response (%) 3.2 3.6 5.2
Results Antibody response at 1 month

  • ChAd3EBO-Z: 70.8%
  • rVSVΔG-ZEBOV-GP: 83.7%
  • Placebo: 2.8%

Antibody response at 12 months

  • ChAd3EBO-Z: 63.5%
  • rVSVΔG-ZEBOV-GP: 79.5%
  • Placebo: 6.8%
Adverse Events Common Adverse Events: injection site reaction (ChAd3-28.5%, rVSVΔG- 30.9%, placebo- 6.8%), headache (ChAd3-25.1%, rVSVΔG- 31.9%, placebo- 16.9%), muscle pain (ChAd3-22.3%, rVSVΔG-26.9%, placebo-13.3%), feverishness (ChAd3-23.9%, rVSVΔG-30.5%, placebo-9.0%), fatigue (ChAd3-14.0%, rVSVΔG-15.4%, placebo-8.8%)
Serious Adverse Events: 6 participants (1.2%) in the ChAd3-EBO-Z group

6 (1.2%) in the rVSVΔG-ZEBOV-GP group, and 8 (1.6%) in the placebo group

* Serious adverse events not specified

Percentage that Discontinued due to Adverse Events: N/A
Study Author Conclusions Both vaccines caused an immune response that was largely sustained after 12 months.

 

The data suggest that both vaccines provide immunity without serious side effects . However, a phase 3 trial was not completed due to the end of the outbreak and a decline in cases; therefore, whether the vaccine was able to prevent Ebola infection is unclear.  Limitations of the trial include no data on children, no laboratory to assess protective immunity, and no evidence on long-term protection of the vaccinations. Children account for 16% of those infected with Ebola in the most recent outbreaks; however, since they were not included in the study, there is no information on the safety and effectiveness in pediatrics. Due to the lack of laboratory parameters that assess long-term protectiveness of this vaccine, objective assessment of long-term immunity may be difficult. Despite the limitations, the study provides preliminary results on the effectiveness of the vaccinations, and may be of  interest in the future to better prepare for outbreaks, especially in the areas of high risk.

References

[1]Ebola Virus Disease. World Health Organization web site. http://www.who.int/mediacentre/factsheets/fs103/en/. Updated June 2017. Accessed December 3, 2017.

[2] 2014-2016 Ebola outbreak in West Africa. Center for Disease Control website. https://www.cdc.gov/vhf/ebola/outbreaks/2014-west-africa/index.html. Updated June 22, 2016. Accessed December 3, 2017.

[3] Kennedy SB, Bolay F, Kieh M, et al. Phase 2 Placebo-Controlled Trial of Two Vaccines to Prevent Ebola in Liberia. N Engl J Med. 2017;377(15):1438-1447.

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