527. Improved Safety Profile by Different Designs of Recombinant HA-flagellin Influenza Candidate Vaccines for HA1 California/07, Novel H1N1
Session: Poster Abstract Session: Influenza Vaccines
Friday, October 21, 2011
Room: Poster Hall B1
Handouts
  • IDSA 32466 Taylor-IDSA 111021.pdf (167.9 kB)
  • Background:  We evaluated 3 novel influenza vaccine constructs consisting of the globular head of the HA1 domain of the A/California/07, Novel H1N1 (VAX128) genetically fused to the TLR5 ligand, flagellin, and produced in E. coli. HA1 was fused to the C-terminus of flagellin in VAX128A, replaced the D3 domain of flagellin in VAX128B or was fused in both positions in VAX128C.

    Methods:  112 healthy subjects 18-49 and 100 adults ≥ 65 years old were enrolled in a double blind, placebo controlled clinical trial conducted at two centers. Vaccines were administered IM at doses ranging from 0.5-20μg. Phase 2 study was performed in 100 subjects 18-64 years old comparing 1.25 and 2.5μg doses. All subjects were followed for safety and sera was tested by hemagglutination-inhibition (HAI) pre- and post-vaccination. Serum C-reactive protein, cytokine levels and anti-flagellin antibody were also measured.

    Results:  Serum antibody responses were seen by HAI after doses as low as 0.5 μg. Doses of 1.25 to 2.5 induced a GMT of 1:250 with over 90% seroconversion and seroprotection. In young adults, the maximum tolerated dose for VAX128A was 8 μg and VAX128B 16μg. VAX128C was safe at 20μg, the highest dose tested. In adults ≥ 65 years, all three vaccines were safe at the highest doses tested of 8, 12 and 20μg for VAX128A, B and C, respectively.

    Conclusion: Altering the configuration of the HA1 and flagellin produced influenza vaccines with a large safety window. VAX128C was well tolerated at the highest dose and was highly immunogenic. The globular head of the influenza HA expressed in a prokaryotic system was able to induce a functional antibody response at low doses.


    Subject Category: I. Adult and Pediatric Vaccines

    David Taylor, MD1, Lynda Tussey, PhD2, John J. Treanor, MD3, Theresa Fitzgerald, MS3, Uma Kavita, PhD2, Langzhou Song, PhD1, Alan Shaw, PhD2 and Thomas Hofstaetter, PhD1, (1)VaxInnate Corporation, Cranbury, NJ, (2)VaxInnate Corp, Cranbury, NJ, (3)University of Rochester, Rochester, NY

    Disclosures:

    D. Taylor, VaxInnate Corp: Employee, Salary

    L. Tussey, VaxInnate Corp: Employee, Salary

    J. J. Treanor, Protein Sciences Corporation: Investigator, Research support

    T. Fitzgerald, None

    U. Kavita, VaxInnate: Employee, Salary

    L. Song, VaxInnate Corp: Employee, Salary

    A. Shaw, VaxInnate Corp: Employee, Salary

    T. Hofstaetter, VaxInnate Corp: Employee, Salary

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