Ebola and Marburg Vaccine Development

1. Ebola and Marburg Vaccine Development Dr Hannah Kibuuka Makerere University Walter Reed Project Presentation at the Uganda Medical Association-Uganda Veterinary Association joint conference. Theme: “Disease Eradication, What Will It Take?”

2. Overview of Presentation • Rationale and challenges for Vaccine development • Strategies and vaccine platforms • Clinical trials on filovirus vaccines • Conclusion

3. Rationale • Ebola and Marburg viruses cause geographically unpredictable and sporadic highly fatal disease outbreaks • Case-fatality rates as high as 90% • Are classified as Category A Bioterrorism agents • No Known cure for infection • Uganda has experienced multiple out breaks since 2000

4. Challenges to vaccine development • Different species of Ebola virus • Sporadic and geographically diverse occurrence of outbreaks? Who is the target population for vaccination? • Fully understanding the correlates of protection • Difficulties in establishing traditional clinical trials in the setting • “Animal use” model to conduct efficacy trials • Limited Interest in industry sponsored studies

5. Strategies for vaccine development • Vaccine given in outbreak situations • Preventive vaccine( prophylactic) • Post exposure treatment • Ideally given as a single immunisation with ability to induce durable immune responses • Prophylactic vaccine platform • Given to first responders, lab personnel, military personnel, international aid workers that respond to disease outbreaks, frontline hospital staff

6. Major vaccine platforms • Replication- competent vectored vaccine • Recombinant Vesicular Stomatitis, Recombinant Human parainfluenza virus 3 • Have only been tested in animal models • Have shown efficacy in animal models as prophylactic vaccine and post exposure treatment • Induction of more durable and longer lasting responses • Require fewer immunisations to confer protection • Challenge: Safety of the vaccines particularly in Immuno-compromised individuals

7. Non replicating vaccines • DNA Vaccines • Tested in animal models and only vaccines tested in clinical trials • Safety profile in clinical trials, given in multiple doses • Ability to induce humoral and cellular immunity • Has less than desirable immunogenicity when used alone • Best used in a prime-boost strategy as a platform for prophylactic vaccine

8. Non replicating vaccines • Combined DNA/rAd5 • Offered 100% protection from ZEBOV and Marburg viremia in non-human primates • Elicits Broad immune responses • With multiple species for Ebola, a multivalent or blended vaccine is desirable • Recent report that a combination expressing ZEBOV and SEBOV provided 100% against a challenge with BEBOV in non human primates • Challenge: Long course of vaccination

9. Non Replicating vaccines • Recombinant Ad 5 vaccine • A single vaccination has provided protection and survival in non human primates therefore more suitable for outbreak response • Challenge: Effect of pre-existing immunity to vaccine efficacy • Different adenovirus serotypes are being tested. • Other modes of delivery such as oral or nasal vaccination • Venezuelan equine encephalitis virus and virus like particles

10. Clinical trials of filovirus vaccines

11. Conclusion • Although several vaccine candidates have been tested in animal studies, only a few have been tested in clinical trials. • DNA Vaccines • have immunogenicity that is less desirable when administered alone • Adding rAd boost enhances its utility • Multiple dosages of DNA/rAd are impractical for outbreaks but regimen is useful for vaccination of individuals with high exposure risk • Development of a vaccine for use in outbreaks is key for endemic countries