Tularemia vaccine: Safety, reactogenicity, “Take” skin reactions, and antibody responses following vaccination with a new lot of the Francisella tularensis live vaccine strain – A phase 2 randomized clinical Trial

Mark J Mulligan; Jack T Stapleton; Wendy A Keitel; Sharon E Frey; Wilbur H Chen; Nadine Rouphael; Srilatha Edupuganti; Allison Beck; Patricia L Winokur; Hana M El Sahly; Shital M Patel; Robert L Atmar; Irene Graham; Edwin Anderson; Samer S El-Kamary; Marcela F Pasetti; Marcelo B Sztein; Heather Hill; Johannes B Goll; DMID 08-0006 Tularemia Vaccine Study Group

doi:10.1016/j.vaccine.2017.07.024

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Tularemia vaccine: Safety, reactogenicity, “Take” skin reactions, and antibody responses following vaccination with a new lot of the Francisella tularensis live vaccine strain – A phase 2 randomized clinical Trial

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Tularemia vaccine: Safety, reactogenicity, “Take” skin reactions, and antibody responses following vaccination with a new lot of the Francisella tularensis live vaccine strain – A phase 2 randomized clinical Trial

Mark J Mulligan, Jack T Stapleton, Wendy A Keitel, Sharon E Frey, Wilbur H Chen, Nadine Rouphael, Srilatha Edupuganti, Allison Beck, Patricia L Winokur, Hana M El Sahly, …

Vaccine, Vol.35(36), pp.4730-4737

08/24/2017

DOI: 10.1016/j.vaccine.2017.07.024

PMCID: PMC5800773

PMID: 28750854

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Abstract

Tularemia is caused by Francisella tularensis, a gram-negative bacterium that has been weaponized as an aerosol. For protection of personnel conducting biodefense research, the United States Army required clinical evaluation of a new lot of tularemia live vaccine strain manufactured in accordance with Current Good Manufacturing Practices. A phase 2 randomized clinical trial compared the new lot (DVC-LVS) to the existing vaccine that has been in use for decades (USAMRIID-LVS). The vaccines were delivered by scarification to 228 participants. Safety, reactogenicity, take and/or antibody levels were assessed on days 0, 1, 2, 8, 14, 28, 56, and 180. Both vaccines were safe and had acceptable reactogenicity profiles during six months of follow-up. There were no serious or grade 3 and 4 laboratory adverse events. Moderate systemic reactogenicity (mostly headache or feeling tired) was reported by ∼23% of participants receiving either vaccine. Injection site reactogenicity was mostly mild itchiness and pain. The frequencies of vaccine take skin reactions were 73% (95% CI, 64, 81) for DVC-LVS and 80% (95% CI, 71, 87) for USAMRIID-LVS. The 90% CI for the difference in proportions was −6.9% (−16.4, 2.6). The rates of seroconversion measured by microagglutination assay on days 28 or 56 were 94% (95% CI, 88, 98; n=98/104) for DVC-LVS and 94% (95% CI, 87, 97; n=103/110) for USAMRIID-LVS (p=1.00). Day 14 sera revealed more rapid seroconversion for DVC-LVS relative to USAMRIID-LVS: 82% (95% CI, 73, 89) versus 55% (95% CI, 45, 65), respectively (p<0.0001). The DVC-LVS vaccine had similar safety, reactogenicity, take and antibody responses compared to the older USAMRIID vaccine, and was superior for early (day 14) antibody production. Vaccination take was not a sensitive surrogate for seroconversion in a multi-center study where personnel at five research clinics performed assessments. ClinicalTrials.gov identifier NCT01150695

Take

LVS

Bacterial

Vaccine

Tularemia

Francisella tularensis

Details

Title: Subtitle: Tularemia vaccine: Safety, reactogenicity, “Take” skin reactions, and antibody responses following vaccination with a new lot of the Francisella tularensis live vaccine strain – A phase 2 randomized clinical Trial
Creators: Mark J Mulligan - The Hope Clinic of the Emory Vaccine Center, Department of Medicine, Division of Infectious Diseases, Emory University School of Medicine, 500 Irvin Court, Suite 200, Decatur, GA 30030, USA
Jack T Stapleton - University of Iowa, SW54-4, GH, 200 Hawkins Drive, Iowa City, IA 52242, USA
Wendy A Keitel - Departments of Molecular Virology and Microbiology, and Medicine, Baylor College of Medicine, Houston, TX, BCM MS 280, One Baylor Plaza, Houston, TX 77030, USA
Sharon E Frey - Division of Infectious Diseases, Allergy and Immunology, Saint Louis University School of Medicine, 1100 South Grand Boulevard, DRC-8, St. Louis, MO 63104, USA
Wilbur H Chen - Center for Vaccine Development, University of Maryland School of Medicine, 685 W. Baltimore St., Suite 480, Baltimore, MD 21201, USA
Nadine Rouphael - The Hope Clinic of the Emory Vaccine Center, Department of Medicine, Division of Infectious Diseases, Emory University School of Medicine, 500 Irvin Court, Suite 200, Decatur, GA 30030, USA
Srilatha Edupuganti - The Hope Clinic of the Emory Vaccine Center, Department of Medicine, Division of Infectious Diseases, Emory University School of Medicine, 500 Irvin Court, Suite 200, Decatur, GA 30030, USA
Allison Beck - The Hope Clinic of the Emory Vaccine Center, Department of Medicine, Division of Infectious Diseases, Emory University School of Medicine, 500 Irvin Court, Suite 200, Decatur, GA 30030, USA
Patricia L Winokur - University of Iowa, SW54-4, GH, 200 Hawkins Drive, Iowa City, IA 52242, USA
Hana M El Sahly - Departments of Molecular Virology and Microbiology, and Medicine, Baylor College of Medicine, Houston, TX, BCM MS 280, One Baylor Plaza, Houston, TX 77030, USA
Shital M Patel - Departments of Molecular Virology and Microbiology, and Medicine, Baylor College of Medicine, Houston, TX, BCM MS 280, One Baylor Plaza, Houston, TX 77030, USA
Robert L Atmar - Departments of Molecular Virology and Microbiology, and Medicine, Baylor College of Medicine, Houston, TX, BCM MS 280, One Baylor Plaza, Houston, TX 77030, USA
Irene Graham - Division of Infectious Diseases, Allergy and Immunology, Saint Louis University School of Medicine, 1100 South Grand Boulevard, DRC-8, St. Louis, MO 63104, USA
Edwin Anderson - Division of Infectious Diseases, Allergy and Immunology, Saint Louis University School of Medicine, 1100 South Grand Boulevard, DRC-8, St. Louis, MO 63104, USA
Samer S El-Kamary - Center for Vaccine Development, University of Maryland School of Medicine, 685 W. Baltimore St., Suite 480, Baltimore, MD 21201, USA
Marcela F Pasetti - Center for Vaccine Development, University of Maryland School of Medicine, 685 W. Baltimore St., Suite 480, Baltimore, MD 21201, USA
Marcelo B Sztein - Center for Vaccine Development, University of Maryland School of Medicine, 685 W. Baltimore St., Suite 480, Baltimore, MD 21201, USA
Heather Hill - The Emmes Corporation, 401 North Washington Street, Suite 700, Rockville, MD 20850, USA
Johannes B Goll - The Emmes Corporation, 401 North Washington Street, Suite 700, Rockville, MD 20850, USA
DMID 08-0006 Tularemia Vaccine Study Group
Resource Type: Journal article
Publication Details: Vaccine, Vol.35(36), pp.4730-4737
DOI: 10.1016/j.vaccine.2017.07.024
PMID: 28750854
PMCID: PMC5800773
NLM abbreviation: Vaccine
ISSN: 0264-410X
eISSN: 1873-2518
Publisher: Elsevier Ltd
Language: English
Date published: 08/24/2017
Academic Unit: Microbiology and Immunology; Infectious Diseases; Medicine Administration; Internal Medicine
Record Identifier: 9984094398702771

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