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  1. Biologics Research Projects

DNA Virus Vaccines and Vectors

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

General Overview

The development of vaccines against viral diseases, such as smallpox, genital herpes, and avian influenza, is a high public health priority. However, in each case, there are issues associated with either safety or effectiveness of available vaccines or those under development for clinical use. To illustrate this point, a few examples: 1) the only licensed vaccine for smallpox is extremely effective, but its use is associated with rare, serious adverse events; 2) there are no licensed vaccines for genital herpes, a common sexually transmitted disease in the United States; and 3) development of effective vaccines for potential pandemic influenza viruses has been slowed by the difficulty in evaluating their efficacy because the number of people who contract this virus remains very low.

Developing safe and effective vaccines against high-priority viral diseases will require an understanding of how the immune system provides protection against such diseases and the development of tools to measure and evaluate vaccine immunogenicity.

This research program focuses on 1) identifying and evaluating viral antigens and vaccination strategies that are key to the development of protective immunity following vaccination; and 2) developing tools to measure and evaluate relevant biomarkers of vaccine immunogenicity.

Our laboratory is working to facilitate development and evaluation of pandemic influenza vaccines as part of the FDA effort in pandemic influenza preparedness. We are also working to identify and evaluate viral antigens and vaccination strategies that are important in the development of protective immunity against DNA viruses such as smallpox and genital herpes.

Both objectives are highly relevant to the CBER public health mission of regulating viral vaccines to ensure their safety and efficacy, and of facilitating development and evaluation of high priority vaccines that impact the public health.

Scientific Overview

The current research focus includes two major objectives: 1) to facilitate development and evaluation of pandemic influenza vaccines, and 2) to identify and evaluate viral antigens and vaccination strategies important for the development of protective immunity against DNA viruses. This research effort includes the development and evaluation of animal models, in vitro assays, and molecular tools necessary for such an evaluation. These studies will provide the tools and understanding necessary for evaluation of candidate vaccines. Major issues being addressed in the effort to facilitate evaluation of pandemic influenza vaccines include the development of new methods to prepare potency reagents, investigating vaccination strategies that can enhance protective immunity to pandemic influenza, development of new tools and methods for determination of potency and evaluation of vaccine responses, and the development of new methods for improving vaccine yields. Major issues being addressed in the effort to facilitate evaluation of DNA virus vaccines include determining the role of individual antigens in the protective response to smallpox vaccination and the development of new methods and assays to quantify the immune response to vaccination.


PLoS One 2017 Jul 27;12(7):e0181999
Generation and characterization of interferon-lambda 1-resistant H1N1 influenza A viruses.
Ilyushina NA, Lugovtsev VY, Samsonova AP, Sheikh FG, Bovin NV, Donnelly RP

PLoS One 2017 Apr 19;12(4):e0175733
Determination of influenza B identity and potency in quadrivalent inactivated influenza vaccines using lineage-specific monoclonal antibodies.
Verma S, Soto J, Vasudevan A, Schmeisser F, Alvarado-Facundo E, Wang W, Weiss CD, Weir JP

Influenza Other Respir Viruses 2016 Sep;10(5):354-60
An overview of the regulation of influenza vaccines in the United States.
Weir JP, Gruber MF

Influenza Other Respir Viruses 2016 Mar;10(2):134-40
A novel approach for preparation of the antisera reagent for potency determination of inactivated H7N9 influenza vaccines.
Schmeisser F, Jing X, Joshi M, Vasudevan A, Soto J, Li X, Choudhary A, Baichoo N, Resnick J, Ye Z, McCormick W, Weir JP

PLoS One 2016 Feb 19;11(2):e0149364
Percutaneous vaccination as an effective method of delivery of MVA and MVA-vectored vaccines.
Meseda CA, Atukorale V, Kuhn J, Schmeisser F, Weir JP

PLoS One 2016 Feb 10;11(2):e0149149
Glycosylation of residue 141 of subtype H7 influenza A hemagglutinin (HA) affects HA-pseudovirus infectivity and sensitivity to site A neutralizing antibodies.
Alvarado-Facundo E, Vassell R, Schmeisser F, Weir JP, Weiss CD, Wang W

PLoS One 2015 Jan 28;10(1):e0117108
Antibodies to antigenic site A of influenza H7 hemagglutinin provide protection against H7N9 challenge.
Schmeisser F, Vasudevan A, Verma S, Wang W, Alvarado E, Weiss C, Atukorale V, Meseda C, Weir JP

Clin Vaccine Immunol 2014 Sep;21(9):1330-8
Glycosylated and nonglycosylated complement control protein of the lister strain of vaccinia virus.
Meseda CA, Kuhn J, Atukorale V, Campbell J, Weir JP

Influenza Other Respir Viruses 2014 Sep;8(5):587-95
A monoclonal antibody-based immunoassay for measuring the potency of 2009 pandemic influenza H1N1 vaccines.
Schmeisser F, Vasudevan A, Soto J, Kumar A, Williams O, Weir JP

PLoS One 2013 Sep 13;8(9):e75014
Heterogeneity of the MDCK cell line and its applicability for influenza virus research.
Lugovtsev VY, Melnyk D, Weir JP

Vaccine 2013 Jul 11;31(32):3209-21
Strengthening the influenza vaccine virus selection and development process: Outcome of the 2nd WHO Informal Consultation for Improving Influenza Vaccine Virus Selection held at the Centre International de Conferences (CICG) Geneva, Switzerland, 7 to 9 December 2011.
Al Busaidy S, Al-Gohary A, Ampofo WK, Bekshin Z, Cerkaoui I, Claes F, Cox NJ, Cracknell W, Cui L, Paiva TM, de Wit M, Diep LDT, Donabedian A, Donis R, Dormitzer PR, Eichelberger M, El Kholy N, Engelhardt O, Engelmann HB, Eropkin MY, Fasce R, Fontaine L, Ghadakchi HF, Ghedin E, Giovanni MY, Golding H, da Silva HC, Gysin R, Hamilton K, Hauge SH, Hay A, Huang S, Hungnes O, Ibrahim SSS, Immamura T, Inglis SC, Kadjo H, Katz J, Kawaoka Y, Kelso A, Khan MI, Kilander A, Klimov A, Kreij K, Kusmiaty D, Linde A, Liu MT, Lupulescu E, Mai LQ, Martinez VR, McCauley J, Meyer Q, Modi R, Mohammadi AA, Mokhtari-Azad T, Mol E, Music T, Nelson K, Neuhaus E, Neumeier ER, Niang MN, Odagiri T, Peiris M, Pohlmann A, Popow-Kraupp T, Trilar KP, Rabadan R, Rambaut A, Robertson JS, Rolls C, Sampurno OD, Savy V, Sawanpanyaltert P, Schmid G, Schweiger B, Shapira S, Shinde V, Shu Y, Siqueira M, Smith D, Spiro D, Stevens J, Takizawa K, Tashiro M, Taylor B, Thomas Y, Tsai T, Van der Werf S, Venter M, Waddell AL, Wan XF, Wang D, Webby R, Weir JP, Wentworth D, Wickramasinghe G, Ye ZP, Zambon M, Ziegler T

PLoS One 2013 Jun 13;8(6):e67984
Effect of the deletion of genes encoding proteins of the extracellular virion form of vaccinia virus on vaccine immunogenicity and protective effectiveness in the mouse model.
Meseda CA, Campbell J, Kumar A, Garcia AD, Merchlinsky M, Weir JP

Influenza Other Respir Viruses 2013 May;7(3):480-90
Neutralizing and protective epitopes of the 2009 pandemic influenza H1N1 hemagglutinin.
Schmeisser F, Friedman R, Besho J, Lugovtsev V, Soto J, Wang W, Weiss C, Williams O, Xie H, Ye Z, Weir JP

Influenza Other Respir Viruses 2012 May;6(3):176-87
Determination of H5N1 vaccine potency using reference antisera from heterologous strains of influenza.
Vodeiko GM, Weir JP

Vaccine 2012 May 14;30(23):3413-22
Production and characterization of mammalian virus-like particles from modified vaccinia virus Ankara vectors expressing influenza H5N1 hemagglutinin and neuraminidase.
Schmeisser F, Adamo JE, Blumberg B, Friedman R, Muller J, Soto J, Weir JP

Biologicals 2012 Jan;40(1):96-9
Application of deglycosylation to SDS PAGE analysis improves calibration of influenza antigen standards.
Harvey R, Hamill M, Robertson JS, Minor PD, Vodeiko GM, Weir JP, Takahashi H, Harada Y, Itamura S, Bamford P, Dalla Pozza T, Engelhardt OG

Influenza Other Respir Viruses 2011 Nov;5(6):438-42
Confronting the next pandemic-Workshop on lessons learned from potency testing of pandemic (H1N1) 2009 influenza vaccines and considerations for future potency tests, Ottawa, Canada, July 27-29, 2010.
Hardy S, Eichelberger M, Griffiths E, Weir JP, Wood D, Alfonso C

J Virol 2011 Sep;85(17):9147-58
Passive immunotherapies protect WRvFire and IHD-J-Luc vaccinia virus infected mice from lethality by reducing viral loads in the upper respiratory tract and internal organs.
Zaitseva M, Kapnick SM, Meseda CA, Shotwell E, King LR, Manischewitz J, Scott J, Kodihalli S, Merchlinsky M, Nielsen H, Lantto J, Weir JP, Golding H

Future Microbiol 2010 Sep;5:1367-82
Third-generation smallpox vaccines: challenges in the absence of clinical smallpox.
Meseda CA, Weir JP

Vaccine 2010 Mar 11;28(12):2442-9
An alternative method for preparation of pandemic influenza strain-specific antibody for vaccine potency determination.
Schmeisser F, Vodeiko GM, Lugovtsev VY, Stout RR, Weir JP

Vaccine 2010 Jan 8;28(3):699-706
Recombinant A27 protein synergizes with modified vaccinia Ankara in conferring protection against a lethal vaccinia virus challenge.
He Y, Meseda CA, Vassell RA, Merchlinsky M, Weir JP, Weiss CD

Virology 2009 Nov 25;394(2):218-26
Changes of the receptor-binding properties of influenza B virus B/Victoria/504/2000 during adaptation in chicken eggs.
Lugovtsev VY, Smith DF, Weir JP

Emerg Infect Dis 2009 Aug;15(8):1252-9
Reproducibility of serologic assays for influenza virus A (H5N1).
Stephenson I, Heath A, Major D, Newman RW, Hoschler K, Junzi W, Katz JM, Weir JP, Zambon MC, Wood JM

Proc Natl Acad Sci U S A 2009 Aug 17;106(35):14802-7
Conversion of MDCK cell line to suspension culture by transfecting with human siat7e gene and its application for influenza virus production.
Chu C, Lugovtsev V, Golding H, Betenbaugh M, Shiloach J

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.