Serious Monkey Business: New Promising Chimpanzee Vaccine For Ebola

Azelia Brown, Mercer University College of Pharmacy

In 2014, for the first time since 1976, the Ebola virus was declared an epidemic with a reported 28,616 cases and 11,130 deaths.  The 2014 Ebola epidemic highlighted the need for a vaccine, as the standard strategies (isolating patients, tracing contacts, and strategies for identifying patients) were not effective in containing the outbreak. [1]

The Ebola virus is classified as a filovirus and is associated with severe hemorrhagic fevers that can result in death. [2]  The wild-type glycoprotein, found in chimpanzees, has elicited an immune response while several other vaccines from clinical trials have displayed poor clinical efficacy. A shorter timeline was developed for the testing and approval of this vaccine due to the ebola epidemic. [3]

Chimpanzee Adenovirus Vector Ebola Vaccine [3]
Design Phase I, open-label, dose escalation, clinical trial; N= 20
Objective To determine the safety, side effect profile, and immunogenicity of an recombinant chimpanzee adenovirus type 3 (cAd3) Ebola virus vaccine
Study Groups Group 1: 2×1010 particle units per injection (n=10)

Group 2: 2×1011 particle units per injection (n=10)

Methods Patients of each group were administered an injection of the vaccine in the deltoid muscle.  The first three participants from each group were provided injections no less than one day apart to monitor for safety (the first three participants of group 1 were administered their vaccines before enrollment began in group 2).  An additional 17 participants were assessed for durability of response.  Laboratory (complete blood counts, activated partial-thromboplastin time, prothrombin time, serum creatinine and alanine aminotransferase) and clinical assessments were used to assess safety.  

At weeks 0, 2, 4, and 8, CD4 and CD8 T cell counts were measured to assess if participants had an immunogenic response to the vaccine.  A successful response was defined as a CD4 or CD8 response to any species of the virus at weeks 2, 4, and 8.  Adenovirus serum neutralization assays were performed at week 0 and 4 to determine neutralization at baseline and post-vaccination. 

Duration 48 weeks
Primary Outcome Measure ELISA glycoprotein titer of 90% over baseline value for each serotype
Baseline Characteristics
Gender Women (55%)

Men (45%)

Mean age, years (range) 37 (25-50)
Results

Antibody response to Zaire Species

Antibody response to Sudan species

Antibody response to Zaire-Guinea species

Group 1

   90%

   70%

   90%

Group 2

   100%

   80%

   90%

The vaccine elicited a glycoprotein antibody titer of greater than 102 and was sustained for greater than 40 weeks.

Adverse Events Common Adverse Events: fever (20% in group 2), asymptomatic prolonged aPTT (10% in group 1; 20% in group 2), asymptomatic neutropenia (10% in group 1; 30% in group 2)
Serious Adverse Events: 0%
Percentage that Discontinued due to Adverse Events: 0%
Study Author Conclusions The vaccine induced antibody responses to Ebola species without any incidence of serious adverse effects.

The vaccine showed longer term antibody response than previous vaccines, even without boosting.  Based on these results, phase 2 and 3 trials have already begun in West Africa.  The mild to moderate neutropenia that was reported as an adverse effect has been attributed to margination, which is a transient innate immune response to vaccines.  The ELISA test results documented here are indicative of “vaccine-take,” which is similar to protection observed in non-human primates. The development of the ebola vaccine is promising, since vaccines for filoviruses are still an area of opportunity.

 

References

  1. Outbreaks chronology: Ebola virus disease. Atlanta: Centers for Disease Control and Prevention, 2014.http://www.cdc.gov/vhf/ebola/outbreaks/history/chronology.html. Published April 14, 2016.
  2. Zampieri CA, Sullivan NJ, Nabel GJ. Immunopathology of highly virulent pathogens: insights from Ebola virus. Nat Immunol 2007;8:1159-1164
  3. Ledgerwood JE, Dezure AD, Stanley DA, et al. Chimpanzee Adenovirus Vector Ebola Vaccine. N Engl J Med. 2017;376(10):928-938.
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