1349. A Phase 1 Randomized, Double-Blind, Dose-Escalation, Placebo-Controlled Study to Assess the Safety, Tolerability and Immunogenicity of Inactivated Streptococcus pneumoniae Whole Cell Vaccine Formulated with Alum (PATH-wSP) in Healthy Adults
Session: Poster Abstract Session: Clinical Trials
Saturday, October 5, 2013
Room: The Moscone Center: Poster Hall C
Posters
  • Poster_final.IDSA.Keech.9.2013.pdf (260.0 kB)
  • Background: Current pneumococcal (Pn) vaccines are serotype-specific, involve complicated and expensive manufacturing processes, and are limited by potential serotype replacement. Additional Pn vaccines that are serotype-independent and inherently affordable are needed.  An inactivated whole cell Pn vaccine (wSP) is designed to meet this need and is hypothesized to work through both T- (IL-17) and B-cell immunity based upon preclinical studies. This first-in-human study evaluated the safety, tolerability, and immunogenicity of wSP in healthy adults.

    Methods: Healthy adults (n=42) were randomized to one of 4 groups: 100 µg (n=10), 300 µg (n=10), or 600 µg (n=10) wSP or saline (n=12, Plc) and underwent a series of 3 vaccinations (vx) at monthly intervals. Follow up was through day (D) 84. Post vx assessments included: 1) solicited reactogenicity events (REs) through D7;  2) chemistry/hematology on D7; 2) adverse events (AEs) through D84; and 3) immunogenicity by assay of antibody, T cells (IL-17), and passive transfer (PT) of protection to mice against invasive challenge with S. pneumoniae.

    Results: wSP was safe and well tolerated at all dose levels. REs (mild/moderate) were more frequent with wSP than Plc (mean duration < 4D) with greatest frequency at 600 µg wSP. Maximum REs (severity/frequency) occurred with the first vx. Injection site pain/tenderness was the most common RE.  Chemistry/hematology values were similar for wSP and Plc at D7 post vx. A total of 45 AEs occurred with 5 possibly related to vx and classified as mild: 4 REs >7D post vx and 1 AE with dysfunctional uterine bleeding (3D). One serious AE occurred, not related to vx.

    Assay for wSP by validated ELISA resulted in high pre-immune sera levels without further increase following vx at any dose. Significant increases (vs. Plc) in immune responses were elicited with the 600 µg dose of wSP for both B- and T-cell responses: IgG levels against individual Pn proteins, IL-17 responses measured by intracellular cytokine staining, and PT of protection to mice upon challenge with S. pneumoniae (increase in % survival and time to moribund state).

    Conclusion: wSP is safe and well tolerated, eliciting Pn-specific IgG, IL-17 and functional Abs by PT. The safety and immunogenicity results in adults supports continued evaluation of wSP in the target population of infants and young children.

    Cheryl Keech, MD/PhD, Vaccine R&D, PATH, Seattle, WA

    Disclosures:

    C. Keech, PATH: Employee, Salary

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