Safety and Immunogenidty of Modified Vaccinia Ankara (ACAM3000): Effect of Dose and Route of Administration

Background. We conducted a clinical trial of the safety and immunogenicity of modified vaccinia Ankara (MVA) to examine the effects of dose and route of administration. Methods. Seventy-two healthy, vaccinia virus-naive subjects received 1 of 6 regimens of MVA (ACAM3000) or placebo consisting of 2 a...

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Bibliographic Details
Published in:The Journal of infectious diseases 2010-05, Vol.201 (9), p.1361-1370
Main Authors: Wilck, Marissa B., Seaman, Michael S., Baden, Lindsey R., Walsh, Stephen R., Grandpre, Lauren E., Devoy, Colleen, Giri, Ayush, Kleinjan, Jane A., Noble, Lizanne C., Stevenson, Kristen E., Kim, Haesook T., Dolin, Raphael
Format: Article
Language:English
Subjects:
Antibodies
Antigens
Dosage
Immune response
Neutralizing antibodies
Placebos
Smallpox
Vaccination
Vaccinia
Vaccinia virus
VIRUSES
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Summary:Background. We conducted a clinical trial of the safety and immunogenicity of modified vaccinia Ankara (MVA) to examine the effects of dose and route of administration. Methods. Seventy-two healthy, vaccinia virus-naive subjects received 1 of 6 regimens of MVA (ACAM3000) or placebo consisting of 2 administrations given 1 month apart. Results. MVA was generally well tolerated at all dose levels and by all routes. More pronounced local reactogenicity was seen with the intradermal and subcutaneous routes than with intramuscular administration. Binding antibodies to whole virus and neutralizing antibodies to the intracellular mature virion and extracellular enveloped virion forms of vaccinia virus were elicited by all routes of MVA administration and were greater for the higher dose by each route. Similar levels of neutralizing antibodies were seen at a 10-fold-lower dose given intradermally (1 × 10⁷ median tissue culture infective doses [TCID₅₀]), compared with responses after 1 × 10⁸ TCID₅₀ given intramuscularly or subcutaneously. T cell immune responses to vaccinia virus were detected by an interferon γ enzyme-linked immunospot assay but had no clear relationship to dose or route. Conclusions. These data suggest that intradermal immunization with MVA provides a dose-sparing effect by eliciting antibody responses similar in magnitude and kinetics to those elicited by the intramuscular or subcutaneous routes but at a 10-fold-lower dose. Trial registration. ClinicalTrials.gov identifier: NCTOO133575.
ISSN:0022-1899
1537-6613