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
- N Engl J Med 2024 Feb 28 [Epub ahead of print]
The end of B/Yamagata influenza transmission--transitioning from quadrivalent vaccines.
Monto AS, Zambon M, Weir JP - Conserv Physiol 2024 Jan 27;12(1):coad102
Bat cellular immunity varies by year and dietary habit amidst land conversion.
DeAnglis IK, Andrews BR, Lock LR, Dyer KE, Yang A, Volokhov DV, Fenton MB, Simmons NB, Downs CJ, Becker DJ - One Health 2023 Dec;17:100633
Expanded diversity of novel hemoplasmas in rare and undersampled Neotropical bats.
Volokhov DV, Lock LR, Dyer KE, DeAnglis IK, Andrews BR, Simonis MC, Stockmaier S, Carter GG, Downs CJ, Fenton MB, Simmons NB, Becker DJ - Front Immunol 2023 Dec 12;14:1281732
Serum proteomics reveals a tolerant immune phenotype across multiple pathogen taxa in wild vampire bats.
Vicente-Santos A, Lock LR, Allira M, Dyer KE, Dunsmore A, Tu W, Volokhov DV, Herrera C, Lei GS, Relich RF, Janech MG, Bland AM, Simmons NB, Becker DJ - Int J Syst Evol Microbiol 2023 Aug;73(8):006015
Streptococcus sciuri sp. nov., Staphylococcus marylandisciuri sp. nov. and Staphylococcus americanisciuri sp. nov., isolated from faeces of eastern grey squirrel (Sciurus carolinensis).
Volokhov DV, Zagorodnyaya TA, Furtak VA, Nattanmai G, Randall L, Jose S, Gao Y, Eisenberg T, Delmonte P, Blom J, Mitchell KK - Int J Syst Evol Microbiol 2023 Jul;73(7):005973
Paracholeplasma manati sp. nov. isolated from Florida manatees (Trichechus manatus latirostris).
Volokhov DV, Furtak VA, Zagorodnyaya TA, Gao Y, Davidson MK - Nat Commun 2023 Jun 9;14(1):3393
Intranasal or airborne transmission-mediated delivery of an attenuated SARS-CoV-2 protects Syrian hamsters against new variants.
Stauft CB, Selvaraj P, D'Agnillo F, Meseda CA, Liu S, Pedro CL, Sangare K, Lien CZ, Weir JP, Starost MF, Wang TT - Curr Microbiol 2023 Jun 24;80(8):253
Neisseria montereyensis sp. nov., isolated from oropharynx of California sea lion (Zalophus californianus): genomic, phylogenetic, and phenotypic study.
Volokhov DV, Zagorodnyaya TA, Furtak VA, Nattanmai G, Randall L, Jose S, Gao Y, Gulland FM, Eisenberg T, Delmonte P, Blom J, Mitchell KK - Influenza Other Respir Viruses 2023 May;17(5):e13152
Neutralizing and protective murine monoclonal antibodies to the hemagglutinin of influenza H5 clades 2.3.2.1 and 2.3.4.4.
Schuele C, Schmeisser F, Orr M, Meseda CA, Vasudevan A, Wang W, Weiss CD, Woerner A, Atukorale VN, Pedro CL, Weir JP - J Med Virol 2023 Mar;95(3):e28673
Distinct in vitro and in vivo neutralization profiles of monoclonal antibodies elicited by the receptor binding domain of the ancestral SARS-CoV-2.
Kwon HJ, Zhang J, Kosikova M, Tang W, Ortega-Rodriguez U, Peng H, Meseda CA, Pedro CL, Schmeisser F, Lu J, Kang I, Zhou B, Davis CT, Wentworth DE, Chen WH, Shriver MC, Barnes RS, Pasetti MF, Weir JP, Chen B, Xie H - Int J Pharm 2023 Feb 5;632:122557
Determining critical overlap concentration of polyethylene oxide to support excipient safety assessment of opioid products.
Smith WC, Qu H, Zheng K, Hyen Baek J, Gao Y, Buehler PW, Feng X, Xu X - Nat Commun 2022 Nov 10;13(1):6792
Intranasal delivery of a rationally attenuated SARS-CoV-2 is immunogenic and protective in Syrian hamsters.
Liu S, Stauft CB, Selvaraj P, Chandrasekaran P, D'Agnillo F, Chou CK, Wu WW, Lien CZ, Meseda CA, Pedro CL, Starost MF, Weir JP, Wang TT - J Virol 2022 Sep;96(18):e0116621
Enhanced in vitro and in vivo potency of a T cell epitope in the Ebola virus glycoprotein following amino acid replacement at HLA-A*02:01 binding positions.
Chabot S, Gimie Y, Obeid K, Kim J, Meseda CA, Konduru K, Kaplan G, Sheng Fowler L, Weir JP, Peden K, Major ME - Front Immunol 2022 Jun 17;13:909297
Validation of a harmonized enzyme-linked-lectin-assay (ELLA-NI) based neuraminidase inhibition assay standard operating procedure (SOP) for quantification of N1 influenza antibodies and the use of a calibrator to improve the reproducibility of the ELLA-NI with reverse genetics viral and recombinant neuraminidase antigens: a FLUCOP collaborative study.
Bernard MC, Waldock J, Commandeur S, Strauß L, Trombetta CM, Marchi S, Zhou F, van de Witte S, van Amsterdam P, Ho S, Hoschler K, Lugovtsev V, Weir JP, Montomoli E, Cox RJ, Engelhardt OG, Friel D, Wagner R, Ollinger T, Germain S, Sediri-Schön H - Antimicrob Agents Chemother 2022 Apr 19;66(4):e0000922
Pleiotropic effects of influenza H1, H3, and B baloxavir-resistant substitutions on replication, sensitivity to baloxavir, and interferon expression.
Hickerson BT, Adams SE, Barman S, Miller L, Lugovtsev VY, Webby RJ, Ince WL, Donnelly RP, Ilyushina NA - Front Physiol 2022 Mar 21;13:845347
ZOOMICS: comparative metabolomics of red blood cells from guinea pigs, humans, and non-human primates during refrigerated storage for up to 42 days.
Bertolone L, Shin HKH, Baek JH, Gao Y, Spitalnik SL, Buehler PW, D'Alessandro A - Int J Syst Evol Microbiol 2022 Jan;72(1):005224
Mycoplasma miroungirhinis sp. nov. and Mycoplasma miroungigenitalium sp. nov., isolated from northern elephant seals (Mirounga angustirostris), Mycoplasma phocoenae sp. nov., isolated from harbour porpoise (Phocoena phocoena), and Mycoplasma phocoeninasale sp. nov., isolated from harbour porpoise and California sea lions (Zalophus californianus).
Volokhov DV, Furtak VA, Blom J, Zagorodnyaya TA, Gao Y, Gulland FM - Viruses 2022 Jan 6;14(1):95
Modulation of HIV replication in monocyte-derived macrophages (MDM) by host antiviral factors secretory leukocyte protease inhibitor and Serpin family C member 1 induced by steroid hormones.
Biswas S, Chen E, Gao Y, Lee S, Hewlett I, Devadas K - NPJ Vaccines 2021 Dec 3;6(1):145
MVA vector expression of SARS-CoV-2 spike protein and protection of adult Syrian hamsters against SARS-CoV-2 challenge.
Meseda CA, Stauft CB, Selvaraj P, Lien CZ, Pedro C, Nuñez IA, Woerner AM, Wang TT, Weir JP - Vaccine 2021 Oct 29;39(45):6573-84
A research and development (R&D) roadmap for influenza vaccines: looking toward the future.
Moore KA, Ostrowsky JT, Kraigsley AM, Mehr AJ, Bresee JS, Friede MH, Gellin BG, Golding JP, Hart PJ, Moen A, Weller CL, Osterholm MT, Influenza Vaccines R&D Roadmap Taskforce, Ampofo W, Barclay W, Cavaleri M, Cohen C, Cowling B, Cox R, Gustm I, Innis B, Kang G, Katz J, Krammer F, Pitisuttithum P, Post D, Rudenko L, Siqueira M, Weir J - NPJ Vaccines 2021 Feb 26;6(1):30
Highly pathogenic avian influenza A/Guangdong/17SF003/2016 is immunogenic and induces cross-protection against antigenically divergent H7N9 viruses.
Radvak P, Kosikova M, Kuo YC, Li X, Garner R, Schmeisser F, Kosik I, Ye Z, Weir JP, Yewdell JW, Xie H - Front Physiol 2020 Oct 23;11:593841
ZOOMICS: comparative metabolomics of red blood cells from old world monkeys and humans.
Bertolone L, Shin HK, Stefanoni D, Baek JH, Gao Y, Morrison EJ, Nemkov T, Thomas T, Francis RO, Hod EA, Zimring JC, Yoshida T, Karafin M, Schwartz J, Hudson KE, Spitalnik SL, Buehler PW, D'Alessandro A - Antimicrob Agents Chemother 2020 Jul;64(7):e00301-20
Laninamivir-interferon-lambda1 combination treatment promotes resistance by influenza A virus more rapidly than laninamivir alone.
Adams SE, Lugovtsev VY, Kan A, Bovin NV, Donnelly RP, Ilyushina NA - 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 - Vaccines 2020 Mar 19;8(1):137
Stability of the HSV-2 US-6 gene in the del II, del III, CP77, and I8R-G1L sites in modified vaccinia virus Ankara after serial passage of recombinant vectors in cells.
Atukorale VN, Weir JP, Meseda CA - 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