Phase 1 Trials of rVSV Ebola Vaccine in Africa and Europe

In August 2014, the World Health Organization (WHO) declared the outbreak of the Ebola virus disease a public health emergency of international concern1. Shortly after, the Canadian government donated a vial of the replication-competent recombinant vesicular stomatitis virus (rVSV)-vectored Zaire ebolavirus (rVSV-ZEBOV) candidate vaccine to the WHO. This vaccine has been studied in nonhuman primates with some promising results, but it has not previously been studied in humans2-4.

Title: Phase 1 Trials of rVSV Ebola Vaccine in Africa and Europe
Design Three open-label, dose escalation phase 1 trials and one randomized, double-blind, controlled phase 1 trial; N= 158
Objective To assess the safety and immunogenicity of various doses of rVSV-ZEBOV in countries with or without previous outbreaks of Ebola virus disease
Study Groups Open-label, dose escalation phase 1 trials

Hamburg:

·      Vaccine, 3 million plaque forming units (PFU) (n= 10)

·      Vaccine, 20 million PFU (n= 10)

 

Lambaréné:

·      Vaccine, 300,000 PFU (n= 20)

·      Vaccine, 3 million PFU (n= 19)

 

Kilifi:

·      Vaccine, 3 million PFU (n= 20)

·      Vaccine, 20 million PFU (n= 20)

 

Randomized, double-blind, controlled phase 1 trial

Geneva:

·      Vaccine, 10 million PFU (n= 35)

·      Vaccine, 50 million PFU (n= 16)

·      Placebo vaccine (n= 8)

Methods Monitoring:

Injection site and systemic reactogenicity and medication use were recorded for 7 days after injection and at follow up (days 14 and 28). Viral loads were detected using a reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assays targeting the VSV nucleoprotein gene. In dose escalation trials, rVSV viral loads were monitored from day 0 to day 28. In Geneva, rVSV viral loads were monitored on days 1, 3, and 7. For immunogenicity, serum samples were assessed at baseline and at 28 and 180 days after injection.

Duration November 10, 2014 to January 19, 2015
Primary Outcome Measure Safety Outcomes and seropositivity
Baseline Characteristics  

Characteristic

 

 

All Participants

(n=158)

Sex-no. %  
Male 110(70)
Female 48(30)
Age-yr  
Mean 36±11
Range 20-59
Race-no %  
Asian 4(3)
Black 78(49)
White 74(47)
Body-mass Index 24±4
Results Immunogenicity:
Study Site and Dose No. of Participants Seropositivity*

no. (%)

P Value for Seropositivity
      Day 0 vs. 28 Day 0 vs. 180
Geneva        
Placebo        
Day 0 8 0    
Day 28 8 0 NA  
Day 180 8 0   NA
10 million PFU        
Day 0 34 8 (24)    
Day 28 34 34 (100) <0.001  
Day 180 33 33 (100)   <0.001
50 million PFU        
Day 0 13 5 (38)    
Day 28 13 13 (100) 0.008  
Day 180 15 13 (100)   0.008
Lambaréné        
300,000 PFU        
Day 0 20 11 (55) 0.004  
Day28 20 20 (100)    
Day180 16 15 (94)   0.03
3 million PFU        
Day 0 19 3 (19) <0.001  
Day 28 19 19 (100)    
Day 180 17 17 (100)   <0.001
Kilifi        
3 million PFU        
Day 0 20 3 (15)    
Day 28 20 20 (100) <0.001  
Day 180 20 20 (100)   <0.001
20 million PFU        
Day 0 0      
Day 28 0 NA NA  
Day 180 20 20 (100)   NA
Hamburg        
3 million PFU        
Day 0 10 0 0.002  
Day 28 10 10 (100)    
Day 180 9 9 (100)   0.004
20 million PFU        
Day 0 10 2 (20) 0.008  
Day 28 10 10 (100)    
Day 180 10 10 (100)   0.008
Adverse Events Common Adverse Events (dose dependent): headache (41.8%), fatigue (35.4%), fever (30%), GI symptoms (14.5%), arthralgia (12%), arthritis (8.2%), maculopapular rash (2%)
Serious Adverse Events: none related to vaccine
Percentage that Discontinued due to Adverse Events: 0%
Study Author Conclusions In these studies, rVSV_ZEBOV was reactogenic but immunogenic after a single dose and warrants further evaluation for safety and efficacy.

The main outcome of this study shows promising results for a possible vaccine for the Ebola virus. Because participants were not followed for an extensive period, further evaluation about the long-term effectiveness of the vaccine are needed. Additionally, the uncommon side effects of the vaccine such as arthritis need to be further evaluated. However, this is a step in the right direction for combating against the Ebola virus.

References

  1. World Health Organization. Ebola Outbreak an International Public Health Emergency. Aug 2014. http://www.who.int
  2. Jones SM, Feldmann H, Stroher U, et al. Live attenuated recombinant vaccine protects nonhuman primates against Ebola and Marbug viruses. Nat Med 2005; 11:786-90.
  3. Geisbert TW, Daddario-Dicaprio KM, Lewis MG, et al. Vesicular stomatitis virus-based ebola vaccine is well-tolerated and protects immunocompromised nonhuman primates. PLoS Pathog 2008;4(11):e10000225.
  4. Geisbert TW, Geisbert JB, Leung A, et al. Single-injection vaccine protects nonhuman primates against infection with Marburg virus and three species of Ebola virus. J Virol 2009;83:7296-304.
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