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A phase I safety and immunogenicity dose escalation trial of plague vaccine, Flagellin/F1/V, in healthy adult volunteers (DMID 08-0066)
- Source :
- Vaccine. 35:6759-6765
- Publication Year :
- 2017
- Publisher :
- Elsevier BV, 2017.
-
Abstract
- Introduction Intentional aerosolization of Yersinia pestis may result in pneumonic plague which is highly fatal if not treated early. 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 8 through 45 years. Vaccine was administered intramuscularly on Days 0 and 28 at a dose of 1, 3, 6 or 10 mcg. Subjects were observed for 4 h after vaccination for cytokine release syndrome. Reactogenicity and adverse events (AE) were collected for 14 and 28 days, respectively, after each vaccination. Serious AE were collected for the entire study. ELISA antibody and cytokines were measured at multiple time points. Subject’s participation lasted 13 months. Results Sixty healthy subjects were enrolled; 52% males, 100% non-Hispanic, 91.7% white and mean age 30.8 years. No severe reactogenicity events occurred; 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 titers (95% CI) after two 10 mcg doses of vaccine were 260.0 (102.6–659.0) and 983.6 (317.3–3048.8), respectively, against F1 and V antigens. The 6 mcg dose group provided similar titers. Titers were low for the placebo, 1 mcg and 3 mcg recipients. A positive antibody dose response was observed to F1, V and flagellin. Vaccine antigen specific serum IgE was not detected. There were no significant rises in serum or cellular cytokine responses and no significant 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. Antibody specific responses to F1, V and flagellin increased as dose increased. Given the results from this trial, testing higher doses of the vaccine may be merited.
- Subjects :
- Adult
Male
Pore Forming Cytotoxic Proteins
0301 basic medicine
Adolescent
Drug-Related Side Effects and Adverse Reactions
Yersinia pestis
030106 microbiology
Dose-Response Relationship, Immunologic
Enzyme-Linked Immunosorbent Assay
Injections, Intramuscular
Young Adult
03 medical and health sciences
Bacterial Proteins
Antigen
medicine
Humans
Child
Antigens, Bacterial
Plague
Plague Vaccine
Reactogenicity
General Veterinary
General Immunology and Microbiology
biology
business.industry
Immunogenicity
Vaccination
Public Health, Environmental and Occupational Health
Antibody titer
Middle Aged
medicine.disease
Antibodies, Bacterial
Healthy Volunteers
Cytokine release syndrome
030104 developmental biology
Infectious Diseases
Oncology
TLR5
Immunology
biology.protein
Cytokines
Molecular Medicine
Plague vaccine
Female
business
Flagellin
Subjects
Details
- ISSN :
- 0264410X
- Volume :
- 35
- Database :
- OpenAIRE
- Journal :
- Vaccine
- Accession number :
- edsair.doi.dedup.....d6a611db6ae7cc6301e26cc7dc98f188