Presentation on theme: "Public Security S&T Symposium 2009"— Presentation transcript:
1Public Security S&T Symposium 2009 Pre-clinical Development of a Nasal Adenovirus-Based Vaccine Against Ebola Virus (CRTI RD)
2PROJECT BACKGROUNDAn ongoing NIH sponsored phase 1 clinical trial is evaluating Adenovirus-based vaccine to stimulate significant immune responses against Ebola virus.Goal: Pre-clinical development of a nasal adenovirus-based vaccine against Ebola virus.We have developed an optimized adenovirus-based Ebola vaccine that can stimulate both mucosal and systemic immune responses following nasal immunization.The first objective is to develop a formulated pre-clinical grade optimized AdHu5 EBOV vaccine.The second objective is to advance the knowledge on immune correlates of protection against EBOV in NHPs.
3Different Vaccine Strategies DNAVacciniaVEE repliconVLPs (Warfield et al. 2007)HPIV3VSVAdenovirusHave successfully protected NHP(Bukreyev et al., 2007)(Jones et al., 2005)(Sullivan et al., 2000)
4ObjectiveTo optimize expression of the ZEBOV glycoprotein from an adenoviral vector and compare it to the CMV driven EboGP Ad vaccine vector.Improving the expression cassetteCodon optimizationImproved CAG promoter
5FIX MMI: Computer control Image created by Robert Voyer, BRI-ACTDSP, JAN. 1998
9Survival and weight loss 28 days post-vaccination VaccineConcentration (IFU/Mouse)Survival (Percentage)Weight Loss (Percentage)Ad-CMVZGP1 x 1071001 x 1061 x 1054017Ad-CAGoptZGP1 x 104Controlna1>25Mice were challenged with a lethal dose (LD50 = 1000) of mouse-adapted ZEBOV
19PROJECT STATUS AND ACCOMPLISHMENTS Significant progress steps related to milestonesComparative evaluation of the first and second generation Ad-Ebo vaccines in mice and guinea pigs.Key Technical Accomplishments, Innovations, Inventions100-fold improvement in protective dose, post-exposure protection and overcoming pre-existing immunity.Potential linkages to projects not defined in the Project Charter.Gene optimization may be beneficial to other vaccine platform such as VSV.
20PROJECT SUMMARY AND CONCLUSIONS The optimized vaccine also fully protected mice against a lethal challenge with ZEBOV at a dose 100 times lower than the minimal dose required to achieve full protection with the first generation vaccine.Complete survival was also achieved 30 minutes post-exposure although weight loss was observed.Higher number of IFN-γ, TNF-α and IL-2 positive CD8 T cells and NAB were detected from splenocytes of Ad-CAGoptZGP immunized mice 6 days post-vaccination when compared to AdCMVZGP immunized mice.Several promising formulations have been identified. Mice vaccinated by the nasal route with these preparations have similar or slightly improved immune responses against Ebola and can survive challenge.Published in: PLoS ONE, 2009;4(4):e5308. Epub 2009 Apr 23.
21PROJECT REVIEW COMMITTEE Core Members:Project Champion: Dr. Harvey ArtsobProject Manager: Dr. Gary KobingerPortfolio Manager: Norm YanofskyNRC Management Representative: Dr. Amine KamenUniversity of Texas Management Representative: Dr. Maria CroyleAssociate Members:Procurement Lead: Daniele Cole / Doris BruneauDeputy Project Manager: Dr. Jim StrongRecording Secretary: Doris Bruneau
22Routes of immunization: protection in mice against 200 LD50 of MA-Ebola virus Intramuscular (I.M.)(%)Intranasal (I.N.)OralVehicleAdHu5-ZGP100100AdHu5-ZGP+ human Ig