Comparison of lyophilized versus liquid modified vaccinia Ankara (MVA) formulations and subcutaneous versus intradermal routes of administration in healthy vaccinia-naïve subjects

Sharon E Frey; Jack T Stapleton; Anna Wald; Patricia Winokur; Srilatha Edupuganti; Lisa A Jackson; Hana El Sahly; Samer S El-Kamary; Kathryn Edwards; Harry Keyserling; Wendy Keitel; Heather Hill; Johannes B Goll; Edwin L Anderson; Irene L Graham; Christine Johnston; Mark Mulligan; Nadine Rouphael; Robert Atmar; Shital Patel; Wilbur Chen; Karen Kotloff; C. Buddy Creech; Paul Chaplin; Robert B Belshe

doi:10.1016/j.vaccine.2015.06.075

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Comparison of lyophilized versus liquid modified vaccinia Ankara (MVA) formulations and subcutaneous versus intradermal routes of administration in healthy vaccinia-naïve subjects

Journal article

Peer reviewed

Comparison of lyophilized versus liquid modified vaccinia Ankara (MVA) formulations and subcutaneous versus intradermal routes of administration in healthy vaccinia-naïve subjects

Sharon E Frey, Jack T Stapleton, Anna Wald, Patricia Winokur, Srilatha Edupuganti, Lisa A Jackson, Hana El Sahly, Samer S El-Kamary, Kathryn Edwards, Harry Keyserling, …

Vaccine, Vol.33(39), pp.5225-5234

09/22/2015

DOI: 10.1016/j.vaccine.2015.06.075

PMID: 26143613

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https://www.ncbi.nlm.nih.gov/pmc/articles/9533873View

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Abstract

•Lyophilized MVA was more immunogenic than the current liquid formulation of MVA.•The lower ID dose of MVA was immunologically non-inferior to the standard SC dose.•The ID route resulted in more erythema and/or induration than the SC route.•The ID route may increase the number of available doses in an emergency situation. Modified vaccinia Ankara (MVA) is being developed as a safer smallpox vaccine and is being placed in the US Strategic National Stockpile (SNS) as a liquid formulation for subcutaneous (SC) administration at a dose of 1×108 TCID50 in a volume of 0.5mL. This study compared the safety and immunogenicity of the standard formulation, dose and route with both a more stable, lyophilized formulation and with an antigen-sparing intradermal (ID) route of administration. 524 subjects were randomized to receive either a full dose of Lyophilized-SC, a full dose of Liquid-SC or 20% (2×107 TCID50 in 0.1mL) of a full dose Liquid-ID MVA on Days 0 and 28. Safety and immunogenicity were followed through 180 days post second vaccination. Among the 3 groups, the proportion of subjects with moderate/severe functional local reactions was significantly different (P=0.0013) between the Lyophilized-SC group (30.3%), the Liquid-SC group (13.8%) and Liquid-ID group (22.0%) only after first vaccination; and for moderate/severe measured erythema and/or induration after any vaccination (P=0.0001) between the Lyophilized-SC group (58.2%), the Liquid-SC group (58.1%) and the Liquid-ID group (94.8%) and the reactions lasted longer in the Liquid-ID group. In the ID Group, 36.1% of subjects had mild injection site skin discoloration lasting ≥6 months. After second vaccination Day (42–208), geometric mean of peak neutralization titers were 87.8, 49.5 and 59.5 for the Lyophilized-SC, Liquid-SC and Liquid-ID groups, respectively, and the maximum number of responders based on peak titer in each group was 142/145 (97.9%), 142/149 (95.3%) and 138/146 (94.5%), respectively. At 180 days after the second vaccination, geometric mean neutralization titers declined to 11.7, 10.2 and 10.4 with only 54.3%, 39.2% and 35.2% of subjects remaining seropositive for the Lyophilized-SC, Liquid-SC and Liquid-ID groups, respectively. Both the Lyophilized-SC and Liquid-ID groups were considered non-inferior (primary objective) to the Liquid-SC group. Transitioning to a lyophilized formulation, which has a longer shelf life, will not negatively impact immunogenicity. In a situation where insufficient vaccine is available, ID vaccination could be used, increasing the number of available doses of vaccine in the SNS 5-fold (i.e., from 20 million to 100 million doses).

IMVAMUNE

Plaque reduction neutralizing antibody

Smallpox

Vaccinia-naïve

Subcutaneous

Intradermal

NCT00914732

Variola

MVA

Lyophilized

ELISA

Details

Title: Subtitle: Comparison of lyophilized versus liquid modified vaccinia Ankara (MVA) formulations and subcutaneous versus intradermal routes of administration in healthy vaccinia-naïve subjects
Creators: Sharon E Frey - Saint Louis University School of Medicine, Department of Internal Medicine, St. Louis, MO, USA
Jack T Stapleton - University of Iowa and Iowa City VA Medical Center, Department of Internal Medicine, Iowa City, IA, USA
Anna Wald - University of Washington and Fred Hutchinson Cancer Research Center, Seattle, WA, USA
Patricia Winokur - University of Iowa and Iowa City VA Medical Center, Department of Internal Medicine, Iowa City, IA, USA
Srilatha Edupuganti - Emory University School of Medicine, Department of Medicine, Division of Infectious Diseases, Atlanta, GA, USA
Lisa A Jackson - Group Health Cooperative, Seattle, WA, USA
Hana El Sahly - Baylor College of Medicine
Samer S El-Kamary - University of Maryland School of Medicine, Department of Epidemiology and Public Health, Center for Vaccine Development, Baltimore, MD, USA
Kathryn Edwards - Vanderbilt Vaccine Research Program, Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, TN, USA
Harry Keyserling - Emory University, Emory Children's Center, Department of Pediatrics, Atlanta, GA, USA
Wendy Keitel - Baylor College of Medicine, Departments of Molecular Virology and Microbiology and Medicine, Houston, TX, USA
Heather Hill - EMMES Corporation, Rockville, MD, USA
Johannes B Goll - EMMES Corporation, Rockville, MD, USA
Edwin L Anderson - Saint Louis University School of Medicine, Department of Internal Medicine, St. Louis, MO, USA
Irene L Graham - Saint Louis University School of Medicine, Department of Internal Medicine, St. Louis, MO, USA
Christine Johnston - University of Washington and Fred Hutchinson Cancer Research Center, Seattle, WA, USA
Mark Mulligan - Emory University School of Medicine, Department of Medicine, Division of Infectious Diseases, Atlanta, GA, USA
Nadine Rouphael - Emory University School of Medicine, Department of Medicine, Division of Infectious Diseases, Atlanta, GA, USA
Robert Atmar - Baylor College of Medicine, Departments of Molecular Virology and Microbiology and Medicine, Houston, TX, USA
Shital Patel - Baylor College of Medicine, Departments of Molecular Virology and Microbiology and Medicine, Houston, TX, USA
Wilbur Chen - University of Maryland School of Medicine, Center for Vaccine Development, Baltimore, MD, USA
Karen Kotloff - University of Maryland School of Medicine, Center for Vaccine Development, Baltimore, MD, USA
C. Buddy Creech - Vanderbilt Vaccine Research Program, Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, TN, USA
Paul Chaplin - Bavarian Nordic GmbH, Martinsried, Germany
Robert B Belshe - Saint Louis University School of Medicine, Department of Internal Medicine, St. Louis, MO, USA
Resource Type: Journal article
Publication Details: Vaccine, Vol.33(39), pp.5225-5234
DOI: 10.1016/j.vaccine.2015.06.075
PMID: 26143613
NLM abbreviation: Vaccine
ISSN: 0264-410X
eISSN: 1873-2518
Publisher: Elsevier Ltd
Grant note: DOI: 10.13039/100013347, name: Institute of Translational Health Sciences, University of Washington, award: HHSN272200800004C, HHSN272200800005C; DOI: 10.13039/100000002, name: National Institutes of Health, award: UL1RR024979; DOI: 10.13039/100000060, name: National Institute of Allergy and Infectious Diseases, award: HHSN272200800008C; DOI: 10.13039/100006108, name: National Center for Advancing Translational Sciences, award: KL2TR000421, TL1TR000422, UL1TR000423; DOI: 10.13039/100007856, name: Baylor College of Medicine, award: HHSN266200400072C, HHSN272200800001C, HHSN272200800007C, HHSN272200800013C; DOI: 10.13039/100010390, name: Saint Louis University
Language: English
Date published: 09/22/2015
Academic Unit: Microbiology and Immunology; Infectious Diseases; Medicine Administration; Internal Medicine
Record Identifier: 9984094213302771

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