DNA Virus Vaccines and Vectors

Principal Investigator: Jerry P. Weir, PhD
Office / Division / Lab: OVRR / DVP / LDV

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Overview

Public Health Issue: Development of vaccines against viral diseases, including such diseases as smallpox, genital herpes, and avian influenza, is an extremely high public health priority. For example, the only licensed vaccine for smallpox is extremely effective, but rare, serious adverse events are associated with its use; there are no licensed vaccines for genital herpes, a common sexually transmitted disease in the United States. Development of effective vaccines for potential pandemic influenza viruses is further confounded by the difficulty of efficacy evaluation in the absence of significant human disease. Thus, development of effective vaccines against high priority viral diseases will require an understanding of the nature of protective immunity, the identification of correlates of protection, and the development of tools for measurement and evaluation of the identified biomarkers of vaccine immunogenicity.

Regulatory Contribution: To facilitate development and licensure of new vaccines against high priority viral diseses (e.g., smallpox, genital herpes, avian influenza), it is important to develop efficacy biomarkers, i.e., to be able to measure and evaluate the ability of a candidate vaccine to elicit a protective immune response. In addition, it will be necessary to be able to measure and compare such a response to vaccines with known protective capacity (e.g., traditional smallpox vaccines) and to be able to measure and compare the immune response of candidate vaccines in animal models (e.g., genital herpes, avian influenza). Finally, DNA virus vectors have great promise as both novel vaccine vectors and as tools for vaccine evaluation.

Research Approach: This research program focuses on identification and evaluation of viral antigens and vaccination strategies which are important for the development of protective immunity following vaccination, and the development of tools for measurement and evaluation of relevant biomarkers of vaccine immunogenicity. This research effort includes the development and evaluation of animal models, in vitro assays, and tools necessary for such an evaluation.

Mission Relevance and Outcomes: These studies will provide the tools and understanding necessary for evaluation of candidate vaccines.

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Publications

Vaccine 2008 Aug 12;26(34):4299-303
FDA/NIH/WHO public workshop on immune correlates of protection against influenza A viruses in support of pandemic vaccine development, Bethesda, Maryland, US, December 10-11, 2007.
Eichelberger M, Golding H, Hess M, Weir J, Subbarao K, Luke CJ, Friede M, Wood D

Clin Vaccine Immunol 2007 Aug;14(8):1032-44
Characterization and use of mammalian-expressed vaccinia virus extracellular membrane proteins for quantification of the humoral immune response to smallpox vaccines.
Garcia AD, Meseda CA, Mayer AE, Kumar A, Merchlinsky M, Weir JP

BMC Biotechnol 2007 May 14;7:22
Incorporation of a lambda phage recombination system and EGFP detection to simplify mutagenesis of Herpes simplex virus bacterial artificial chromosomes.
Schmeisser F, Weir JP

J Med Virol 2007 Apr 24;79(6):791-802
Microarray assay for evaluation of the genetic stability of modified vaccinia virus Ankara B5R gene.
Laassri M, Meseda CA, Williams O, Merchlinsky M, Weir JP, Chumakov K

Viral Immunol 2006 Summer;19(2):250-259
Evaluation of a Needle-Free Delivery Platform for Prime-Boost Immunization with DNA and Modified Vaccinia Virus Ankara Vectors Expressing Herpes Simplex Virus 2 Glycoprotein D.
Meseda CA, Stout RR, Weir JP

Hum Gene Ther 2006 Jan;17(1):93-104
Cloning of Replication-Incompetent Herpes Simplex Viruses as Bacterial Artificial Chromosomes to Facilitate Development of Vectors for Gene Delivery into Differentiated Neurons.
Schmeisser F, Weir JP

Virology 2005 Dec 5;343(1):128-40
Identification and preliminary characterization of vaccinia virus (Dryvax) antigens recognized by vaccinia immune globulin.
Jones-Trower A, Garcia A, Meseda CA, He Y, Weiss C, Kumar A, Weir JP, Merchlinsky M

Virology 2005 Sep 1;339(2):164-75
Enhanced immunogenicity and protective effect conferred by vaccination with combinations of modified vaccinia virus Ankara and licensed smallpox vaccine Dryvax in a mouse model.
Meseda CA, Garcia AD, Kumar A, Mayer AE, Manischewitz J, King LR, Golding H, Merchlinsky M, Weir JP

J Infect Dis 2005 Feb 1;191(3):372-81
Smallpox vaccine does not protect macaques with AIDS from a lethal monkeypox virus challenge.
Edghill-Smith Y, Bray M, Whitehouse CA, Miller D, Mucker E, Manischewitz J, King LR, Robert-Guroff M, Hryniewicz A, Venzon D, Meseda C, Weir J, Nalca A, Livingston V, Wells J, Lewis MG, Huggins J, Zwiers SH, Golding H, Franchini G.

Virology 2004 Jan 5;318(1):420-8
DNA immunization with a herpes simplex virus 2 bacterial artificial chromosome.
Meseda CA, Schmeisser F, Pedersen R, Woerner A, Weir JP