srinivas vido-intervac
TRANSCRIPT
NOVEL STRATEGIES FOR IMMUNIZATION AGAINST PERTUSSIS AND RSV INFECTIONS
Srinivas Garlapati
Vaccine and Infectious Disease OrganizationSaskatoon, Canada
A novel adjuvant platform for neonates
Polyphos-phazenes
Delivery of Antigen
HostDefense Peptides
Recruitment
CpG ODN
Immune stimulation
Antigen
Platform technology: Pertussis, RSV, others….
PCEP particle formulation by Ion-bridging with poly-amines
Single step process by simple mixing PCEP with natural poly-amine Chitosan or synthetic poly-ally-amine hydrochloride (PAH) – FDA approved
NaCl-CaCl2 PAH
Chitosan
PCEP- CaCl2 MPs
PCEP- PAH MPs
PCEP- CHIT MPs
PCEP particle uptake by DCsPCEP particle uptake by DCs
Garlapati et al manuscript in submission
Non-Replicating RSV vaccines need TLR Adjuvant
Immune response FI-RSV Reason Read outHumoral response Low Avidity Non-neutralizing Ab-
Ag complexes,Complement Activation,Immune pathology
ELISA-Urea Wash reduces AbsorbanceHigh virus titersHigh Ab/VNT RatioLow IgG2a/IgG1 Ratio
Secretory Antibodies Low IgA Parenteral route Low IgA AbsCytokines Pro-inflammatory
IL1β & IL-15Th2 IL-4, IL-5, IL-13ChemokinesMIP1β, MCP-1, IL-8
Eosinophila,Peri-vasculitisPeri-bronchiolitisBroncho-constrictionMucus
CD4+ T cells High Prolonged innate immune responses,Suppress CD8+ T cells
CD8+ T-cells Low Defective viral clearancd
High virus shedding
RSV VACCINE PIPELINE
Discovery Pre-Clinical Phase-I Phase-II Phase-III2020
MEDI-559MEDI-534 (PIV3)
Novavax VLP F & G
PEV4 (virosome)
Protollin- RSV
RSV287Nanobio RSV
Sendai Virus vectorAlpha Virus vector
Virosomes P3CSK4rRSVΔG
DNA electoporation
Adenovirus vector
0 21 44 48 50
Immunize Boost Challenge
Kill 1
Kill 2
Spleens - ELISPOTLung-Fragment culturesBAL
Groups
1.Saline/RSV challenge2.Ag IN3.Ag Triple Combo SOL IN4.Ag Triple Combo MP IN5.Ag IM6.Ag Triple Combo SOL IM7.Ag Triple Combo MP IM
Triple Combo formulation with ΔF protein
Viral SheddingLung Cytokines
Acknowledgements….Acknowledgements….
Nelson EngGael AurayTadele KirosRachelle BuchananStacy StromMonika PolewiczAleksandra GraciaLaura LatimerMarlene SniderRavinder Garg
Volker GerdtsLorne BabiukAndrew PotterSylvia v.d. HurkHeather Wilson George MutwiriJim HolmstromHugh Townsend
VIDO
Funding: - B. & M. Gates Foundation - Canadian Institute of Health Research - Krembil Foundation - National Science and Engineering Research Council - Saskatchewan Health Research Foundation
Animal CareBarry WalkerSherryOthers…