Vaxcyte Corporate Presentation

15 PCVs Overcome the Limitations of Polysaccharide-Only Vaccines PCV Efficacy Driven by T-Cell Epitopes on Diphtheria Toxin Protein Carrier - CRM 197 (1) Polysaccharide YYX PS-Only Vaccine PNEUMOVAX23 Independent B cells Antibody (no memory) B cell T-Cell Dependent Conjugated protein Prevnar 13 PCVs Pneumococcal 13-vdent Conjugate Vaccine Diphtheria CRM, Protein) Synflorix ON Target Effect B Cells Targeting Polysaccharide T Cell 83 T Cells T-cell help Fi イイ Antibody + memory • Broad Coverage But Limited Protection in Adults - Not Boostable - B Cells Targeting Protein Carrier OFF Target Effect イイ Narrow Coverage But Highly Effective in Adults & Infants - Boostable - Pneumococcal capsular polysaccharides (PS) antigens lead to: • - Transient Ab responses (IgM) protect against sepsis, but not pneumonia No T-cell mediated memory responses, thus no boost Hyporesponsive effect inhibits ability to boost PCVs post-prime Note: Graphics adapted from Strugnell et al, Understanding Modern Vaccines, Vol 1, Issue 1, 61-88. (1) Protein carrier in Prevnar 13 is a modified form of diphtheria toxin (CRM 197). Conjugation of PS to protein carrier leads to: Enhanced Ab responses (IgG) that protect against pneumonia - T cell-mediated memory to provide boostable, durable protection Characteristic interstrand crosslinked matrix-like structures о

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