718. A Randomized, Multi-Center Trial to Evaluate the Safety and Immunogenicity of Staphylococcus aureus Toxoids, rAT and rLukS-PV, in Healthy Volunteers
Session: Poster Abstract Session: Vaccine Studies, Adjuvants, and Discovery
Friday, October 21, 2011
Room: Poster Hall B1
Background: The safety and immunogenicity of recombinant Staphylococcus aureus candidate vaccine antigens alpha toxoid (rAT) and a sub-unit of Panton-Valentine leukocidin (rLukS-PV) are unknown.

Methods: This randomized phase I-II dose-escalation, double-blind, placebo-controlled study enrolled subjects into one of 11 treatment cohorts of 16 subjects each: monovalent rAT or rLukS-PV at dosages of 10, 25, 50, and 100 µg and bivalent rAT:rLukS-PV at dosages of 10:10, 25:25, and 50:50 µg. Subjects in the 50:50 µg bivalent treatment cohort received a second injection at day 84. Incidence and severity of reactogenicity through seven days and adverse events through six months were summarized and compared between vaccine and placebo recipients. Geometric mean serum concentrations (GMC) of anti-rAT and anti-rLukS-PV IgG were assessed by enzyme-linked immunosorbent assay (ELISA) on days 0, 14, 28, and 84 (and 98 and 112 for booster recipients).

Results: Overall 176 subjects were vaccinated. The median age was 31 years (range, 18-55), and 66% were male. Seventy-seven percent of vaccine recipients experienced ≥1 reactogenicity event compared with 55% of placebo recipients (p =0.006). However, 77% of reactogenicity events were mild, and 19% were moderate in severity. Seventy percent of AEs were mild, and the incidence and severity of AEs were similar for vaccine and placebo recipients. For the bivalent treatment cohorts the GMC (±SD) on day 28 for 10, 25, and 50µg dosages were as follows: rAT- 50.2 EU/mL (±2.51), 129 EU/mL (±2.35), and 223 EU/mL (±2.14), respectively (overall, p <0.001); rLukS-PV- 31.2 EU/mL (±3.22), 68.1 EU/mL (±4.73), and 108 EU/mL (±2.66), respectively (overall, p=0.021). The proportion of those achieving a 2-fold or greater increase in GMC for the 50:50 µg bivalent treatment cohort was 100% for rAT and 83.3% for rLukS-PV. Antibody responses to both antigens persisted through day 84 with no clear effect from the second injection.

Conclusion: Further clinical investigation of rAT and rLukS-PV for potential use in a vaccine for the prevention of S. aureus infections is warranted as both antigens were well-tolerated and immunogenic.


Subject Category: I. Adult and Pediatric Vaccines

Michael Landrum, MD1,2, Tahaniyat Lalani, MD1, Minoo Niknian, PhD3, Jason Maguire, MD4, Duane Hospenthal, MD, PhD2, Ali Fattom, PhD3, Kimberly Taylor, PhD3, Jamie Fraser, MPH1, Kenneth Wilkins, PhD1, Michael Ellis, MD5, Paul Kessler, MD3, Raafat Fahim, PhD3 and David Tribble, MD, DrPH1, (1)Infectious Disease Clinical Research Program, Uniformed Services University, Bethesda, MD, (2)Brooke Army Medical Center, Fort Sam Houston, TX, (3)Nabi Biopharmaceuticals, Rockville, MD, (4)Naval Medical Center, Portsmouth, VA, (5)Uniformed Services University of the Health Sciences, Bethesda, MD

Disclosures:

M. Landrum, None

T. Lalani, None

M. Niknian, Nabi Biopharmaceuticals: Employee, Salary

J. Maguire, None

D. Hospenthal, None

A. Fattom, Nabi Biopharmaceuticals: Employee, Salary

K. Taylor, Nabi Biopharmaceuticals: Employee, Salary

J. Fraser, None

K. Wilkins, None

M. Ellis, Forest Laboratories: Speaker's Bureau, Speaker honorarium

P. Kessler, Nabi Biopharmaceuticals: Employee, Salary

R. Fahim, Nabi Biopharmaceuticals: Employee, Salary

D. Tribble, None

Findings in the abstracts are embargoed until 12:01 a.m. EST Thursday, Oct. 20 with the exception of research findings presented at IDSA press conferences.