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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.


Publications

Influenza Other Respir Viruses 2020 Mar;14(2):237-43
Meeting report and review: immunological assays and correlates of protection for next-generation influenza vaccines.
Krammer F, Weir JP, Engelhardt O, Katz JM, Cox RJ

Antiviral Res 2019 Sep;169:104539
Effect of influenza H1N1 neuraminidase V116A and I117V mutations on NA activity and sensitivity to NA inhibitors.
Adams SE, Lee N, Lugovtsev VY, Kan A, Donnelly RP, Ilyushina NA

PLoS One 2019 Sep 12;14(9):e0222436
Generation of a protective murine monoclonal antibody against the stem of influenza hemagglutinins from group 1 viruses and identification of resistance mutations against it.
Wang W, Vassell R, Song HS, Chen Q, Keller PW, Verma S, Alvarado-Facundo E, Wan H, Schmeisser F, Meseda CA, Weir JP, Weiss CD

PLoS One 2018 May 9;13(5):e0196771
Anti-neuraminidase antibodies against pandemic A/H1N1 influenza viruses in healthy and influenza-infected individuals.
Desheva Y, Sychev I, Smolonogina T, Rekstin A, Ilyushina N, Lugovtsev V, Samsonova A, Go A, Lerner A

PLoS One 2018 Apr 9;13(4):e0195525
The use of plant lectins to regulate H1N1 influenza A virus receptor binding activity.
Lee N, Khalenkov AM, Lugovtsev VY, Ireland DD, Samsonova AP, Bovin NV, Donnelly RP, Ilyushina NA

Influenza Other Respir Viruses 2018 Mar;12(2):250-8
Potency determination of inactivated H7 influenza vaccines using monoclonal antibody-based ELISA and biolayer interferometry assays.
Vasudevan A, Woerner A, Schmeisser F, Verma S, Williams O, Weir JP

Influenza Other Respir Viruses 2018 Mar;12(2):195-201
Standardisation of inactivated influenza vaccines--learning from history.
Wood JM, Weir JP

Sci Rep 2018 Mar 29;8(1):5364
Immunogenicity and protection against influenza H7N3 in mice by modified vaccinia virus Ankara vectors expressing influenza virus hemagglutinin or neuraminidase.
Meseda CA, Atukorale V, Soto J, Eichelberger MC, Gao J, Wang W, Weiss CD, Weir JP

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