Viral DNA Vaccines
Guest Editor: Karin Mölling, Zurich

Paper

Plasmid DNA Vaccines: Tissue Distribution and Effects of DNA Sequence, Adjuvants and Delivery Method on Integration into Host DNA
Sujata Manam, Brian J. Ledwith, Amy B. Barnum, Philip J. Troilo, Cindy J. Pauley, Laural B. Harper, Thomas G. Griffiths II, Zhutian Niu, Lyudmila Denisova, Thy T. Follmer, Stephen J. Pacchione, Zhibin Wang, Carolann M. Beare, Walter J. Bagdon, Warren W. Nichols

Department of Safety Assessment, Merck Research Laboratories, West Point, Pa., USA

Address of Corresponding Author

Intervirology 2000;43:273-281 (DOI: 10.1159/000053994)

  Key Words

• DNA vaccine
• Plasmid
• Recombination
• HIV
• Human papilloma virus
• Influenza

  Abstract

A variety of factors could affect the frequency of integration of plasmid DNA vaccines into host cellular DNA, including DNA sequences within the plasmid, the expressed gene product (antigen), the formulation, delivery method, route of administration, and the type of cells exposed to the plasmid. In this report, we examined the tissue distribution and potential integration of plasmid DNA vaccines following intramuscular administration in mice and guinea pigs. We compared needle versus Biojector (needleless jet) delivery, examined the effect of aluminum phosphate adjuvants, compared the results of different plasmid DNA vaccines, and tested a gene (the human papilloma virus E7 gene) whose protein product is known to increase integration frequency in vitro. Six weeks following intramuscular injection, the vast majority of the plasmid was detected in the muscle and skin near the injection site; lower levels of plasmid were also detected in the draining lymph nodes. At early time points (1-7 days) after injection, a low level of systemic exposure could be detected. Occasionally, plasmid was detected in gonads, but it dissipated rapidly and was extrachromosomal - indicating a low risk of germline transmission. Aluminum phosphate adjuvant had no effect on the tissue distribution and did not result in a detectable increase in integration frequency. Biojector delivery, compared with needle injection, greatly increased the uptake of plasmid (particularly in skin at the injection site), but did not result in a detectable increase in integration frequency. Finally, injection of a plasmid DNA vaccine containing the human papilloma virus type 16 E7 gene, known to increase integration in vitro, did not result in detectable integration in mice. These results suggest that the risk of integration following intramuscular injection of plasmid DNA is low under a variety of experimental conditions.

Copyright © 2001 S. Karger AG, Basel

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  Author Contacts

Sujata Manam, PhD
Merck Research Laboratories
West Point, PA 19486 (USA)
Tel. +1 215 652 7494, Fax +1 215 652 7758
E-Mail sujata_manam@merck.com

  Article Information

Number of Print Pages : 9
Number of Figures : 0, Number of Tables : 8, Number of References : 21

  Publication Details

Intervirology (International Journal of Basic and Medical Virology)
Founded 1973 by J.L. Melnick; continued by F. Rapp (1986-1990); M.J. Buchmeier and C.R. Howard (1991-1993)

Vol. 43, No. 4-6, Year 2000 (Cover Date: July-December 2000 (Released February 2001))

Journal Editor: Rüdiger W. Braun, Stuttgart
ISSN: 0300-5526 (print), 1423-0100 (Online)

For additional information: http://www.karger.com/journals/int

  Drug Dosage / Copyright

Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.