899. A Phase I Safety and Immunogenicity Dose Escalation Trial of Plague Vaccine, Flagellin/F1/V, In Healthy Adult Volunteers (DMID 08-0066)
Session: Poster Abstract Session: Clinical Trials
Friday, October 9, 2015
Room: Poster Hall

Background: Yersinia pestis, a Class A agent of bioterrorism, is the etiologic agent of plague. Intentional aerosolization of Y. pestis (YP) will result in pneumonic plague which is highly fatal if not treated within hours.  

Methods: We conducted a phase 1 randomized, double blind (within each group), placebo controlled, dose escalation trial to evaluate a plague vaccine, Flagellin/F1/V, in healthy adults aged 18-49.  Flagellin (salmonella origin)/F1/V recombinant fusion protein (F1 and V were YP antigens and flagellin served as the carrier and adjuvant) vaccine was given intramuscularly on Days 0 and 28 at a dose of 1, 3, 6 or 10 μg.  Subjects remained in an observation unit in the hospital for 4 hours after vaccination to observe for cytokine release syndrome.  Reactogenicity was collected for 14 days and adverse events (AE) were collected for 28 days after each vaccination.  Serious AEs were collected for the entire study.  ELISA antibody and cytokines were measured at multiple time points during the study.  

Results: Sixty healthy subjects were enrolled; 52% males, 100% non-Hispanic, 91.7% white and mean age 30.8 years (range 19 – 48). There were no severe reactogenicity events; most AE were mild. No serious AE related to vaccine occurred. A dose response effect was observed to F1, V and flagellin. The peak ELISA IgG antibody concentrations (95% CI) for the 10 μg dose were 65.5 (28.2 - 151.8), 181.6 (49.7 - 664.4) and 272.4 (194.7 - 381.0), respectively, and ≤ 25 for respective placebo recipients (See Table).    Serum IgE was not detected.  There were no significant rises in serum or cellular cytokine responses and no additional IgG increase to flagellin after the second dose.

Conclusion:  The flagellin/F1/V vaccine exhibited a dose dependent increase in immunogenicity and was well tolerated at all doses.  There was no evidence for cytokine release syndrome. Given the results from this trial, testing higher doses of the vaccine is merited.

 

Peak ELISA IgG Antibody Concentrations (95% CI)

Dose

1 µg

3 µg

6 µg

10µg

Placebo

F1

25.1 (17.8 - 35.5)

38.2 (19.7 - 74.0)

60.8

(38.7 - 95.4)

65.5 (28.2 - 151.8)

22.8

(16.7 - 31.1)

V

35.9 (21.5 -60.0)

60.8 (23.3 -158.3)

173.6 119.8 - 251.5)

181.6 (49.7 - 664.4)

20.0

(-)

Flagellin

43.8 (27.9 -68.7)

88.5

(51.9 - 150.9)

144.7

(79.9 - 261.9)

272.4

(194.7 - 381.0)

25.0 ( - )

 

Sharon E Frey, MD1, Kathleen Lottenbach, MS1, Irene Graham, MD1, Edwin Anderson, MD1, Kanwaldeep Bajwa, MPH2, Ryan May, PhD2, Steven B Mizel, PhD3, Aaron H Graff, BS3 and Robert B Belshe, MD1, (1)Internal Medicine, Division of Infectious Diseases, Saint Louis University, Saint Louis, MO, (2)Emmes, Rockville, MD, (3)Department of Microbiology & Immunology, Wake Forest University School of Medicine, Winston-Salem, NC

Disclosures:

S. E. Frey, National Institute of Health Vaccine Treatment Evaluation Unit: Investigator , Salary

K. Lottenbach, National Institute of Health Vaccine Treatment Evaluation Unit: Employee , Contract # HHSN272200800003C Site Reference # N01-AI-80003

I. Graham, National Institute of Health Vaccine Treatment Evaluation Unit: Employee , Contract # HHSN272200800003C Site Reference # N01-AI-80003

E. Anderson, National Institute of Health Vaccine Treatment Evaluation Unit: Employee , Contract # HHSN272200800003C Site Reference # N01-AI-80003

K. Bajwa, National Institute of Health Vaccine Treatment Evaluation Unit: Employee , Contract # HHSN272200800003C Site Reference # N01-AI-80003

R. May, National Institute of Health Vaccine Treatment Evaluation Unit: Employee , Contract # HHSN272200800003C Site Reference # N01-AI-80003

S. B. Mizel, None

A. H. Graff, None

R. B. Belshe, National Institute of Health Vaccine Treatment Evaluation Unit: Investigator , Contract # HHSN272200800003C Site Reference # N01-AI-80003

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