Skip to main content
  • ASM
    • Antimicrobial Agents and Chemotherapy
    • Applied and Environmental Microbiology
    • Clinical Microbiology Reviews
    • Clinical and Vaccine Immunology
    • EcoSal Plus
    • Infection and Immunity
    • Journal of Bacteriology
    • Journal of Clinical Microbiology
    • Journal of Microbiology & Biology Education
    • Journal of Virology
    • mBio
    • Microbiology and Molecular Biology Reviews
    • Microbiology Resource Announcements
    • Microbiology Spectrum
    • Molecular and Cellular Biology
    • mSphere
    • mSystems
  • Log in
  • My alerts
  • My Cart

Main menu

  • Home
  • Articles
    • Current Issue
    • Accepted Manuscripts
    • COVID-19 Special Collection
    • Minireviews
    • JVI Classic Spotlights
    • Archive
  • For Authors
    • Submit a Manuscript
    • Scope
    • Editorial Policy
    • Submission, Review, & Publication Processes
    • Organization and Format
    • Errata, Author Corrections, Retractions
    • Illustrations and Tables
    • Nomenclature
    • Abbreviations and Conventions
    • Publication Fees
    • Ethics Resources and Policies
  • About the Journal
    • About JVI
    • Editor in Chief
    • Editorial Board
    • For Reviewers
    • For the Media
    • For Librarians
    • For Advertisers
    • Alerts
    • RSS
    • FAQ
  • Subscribe
    • Members
    • Institutions
  • ASM
    • Antimicrobial Agents and Chemotherapy
    • Applied and Environmental Microbiology
    • Clinical Microbiology Reviews
    • Clinical and Vaccine Immunology
    • EcoSal Plus
    • Infection and Immunity
    • Journal of Bacteriology
    • Journal of Clinical Microbiology
    • Journal of Microbiology & Biology Education
    • Journal of Virology
    • mBio
    • Microbiology and Molecular Biology Reviews
    • Microbiology Resource Announcements
    • Microbiology Spectrum
    • Molecular and Cellular Biology
    • mSphere
    • mSystems

User menu

  • Log in
  • My alerts
  • My Cart

Search

  • Advanced search
Journal of Virology
publisher-logosite-logo

Advanced Search

  • Home
  • Articles
    • Current Issue
    • Accepted Manuscripts
    • COVID-19 Special Collection
    • Minireviews
    • JVI Classic Spotlights
    • Archive
  • For Authors
    • Submit a Manuscript
    • Scope
    • Editorial Policy
    • Submission, Review, & Publication Processes
    • Organization and Format
    • Errata, Author Corrections, Retractions
    • Illustrations and Tables
    • Nomenclature
    • Abbreviations and Conventions
    • Publication Fees
    • Ethics Resources and Policies
  • About the Journal
    • About JVI
    • Editor in Chief
    • Editorial Board
    • For Reviewers
    • For the Media
    • For Librarians
    • For Advertisers
    • Alerts
    • RSS
    • FAQ
  • Subscribe
    • Members
    • Institutions
Vaccines and Antiviral Agents

Comparative Efficacy of Recombinant Modified Vaccinia Virus Ankara Expressing Simian Immunodeficiency Virus (SIV) Gag-Pol and/or Env in Macaques Challenged with Pathogenic SIV

Ilnour Ourmanov, Charles R. Brown, Bernard Moss, Miles Carroll, Linda Wyatt, Liuobov Pletneva, Simoy Goldstein, David Venzon, Vanessa M. Hirsch
Ilnour Ourmanov
Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, Rockville, Maryland 20852, and
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Charles R. Brown
Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, Rockville, Maryland 20852, and
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Bernard Moss
Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, and
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Miles Carroll
Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, and
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Linda Wyatt
Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, and
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Liuobov Pletneva
Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, Rockville, Maryland 20852, and
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Simoy Goldstein
Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, Rockville, Maryland 20852, and
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
David Venzon
Biostatistics and Data Management Section, National Cancer Institute, Bethesda, Maryland 20892
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Vanessa M. Hirsch
Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, Rockville, Maryland 20852, and
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
DOI: 10.1128/JVI.74.6.2740-2751.2000
  • Article
  • Figures & Data
  • Info & Metrics
  • PDF
Loading

Article Figures & Data

Figures

  • Tables
  • Fig. 1.
    • Open in new tab
    • Download powerpoint
    Fig. 1.

    Representation of recombinant MVA virus genomes. Insertion of the expression cassette consisting of the sequences coding the SIVsmH-4 env precursor regulated by the synthetic early-late promoter (S.E/L) and the β-gal gene regulated by the vaccinia virus early-late P7.5 promoter is indicated by dashed lines to the site of deletion II within the MVA genome. Insertion of a cassette containing the sequences coding the SIVsmH-4gag-pol precursor regulated by the S.E/L promoter and the GUS gene regulated by the P7.5 promoter is indicated by dashed lines to the site of deletion III. The directions of promoters and open reading frames are indicated.

  • Fig. 2.
    • Open in new tab
    • Download powerpoint
    Fig. 2.

    Expression of SIV proteins in monkey cell line BS-C-1 infected with recombinant MVA viruses. Radioimmunoprecipitation of viral proteins from culture supernatants (panels A and B) and cell extracts (panel C) of BS-C-1 monkey cells infected with different MVA-SIV recombinant viruses. Extracts shown in panel A were immunoprecipitated with plasma from an SIV-infected macaque, and extracts shown in panels B and C were immunoprecipitated with a macaque SIVsm-gp120-specific monoclonal antibody, IgG-201 (23). Lanes 1, immunoprecipitation from mock-infected cells; lanes 2, cells infected with nonrecombinant MVA; lanes 3, recombinant MVA-env; lanes 4, original MVA-SIV recombinant virus; lanes 5, MVA-gag-pol-env; lanes 6, MVA-gag-pol. Molecular mass markers are listed at the right in kilodaltons.

  • Fig. 3.
    • Open in new tab
    • Download powerpoint
    Fig. 3.

    Production of SIV-like particles from BSC-1 cells 24 h after infection with the MVA-gag-pol-envrecombinant virus. Electron micrograph of infected cells with immature and mature SIV-like particles (panel A; magnification, ×54,000) and detailed pictures of mature VLPs (panel B; magnification, ×85,000) and stages of VLPs budding from the cell surface and maturing (panel C; magnification, ×68,000).

  • Fig. 4.
    • Open in new tab
    • Download powerpoint
    Fig. 4.

    Anti-SIVsmH-4 gp130 ELISA antibody titers in sera of immunized and control macaques. Six macaques per group were inoculated four times (open diamonds) with recombinant or nonrecombinant MVA and challenged 4 weeks later with SIVsmE660 (filled diamonds). Serial dilutions of plasma were incubated with recombinant SIVsmH-4 gp130 bound to microtiter plates treated by lectin from G. nivalis. End-point titers were defined as the reciprocal of the highest sera dilution that gave an optical absorbance at least two standard deviations greater in value than average values obtained with negative control sera.

  • Fig. 5.
    • Open in new tab
    • Download powerpoint
    Fig. 5.

    Plasma viral load in immunized and control macaques after challenge with uncloned SIVsmE660. Sequential levels of plasma viral RNA over the first 45 weeks after SIV challenge are shown for animals immunized prior to challenge with MVA-gag-pol, MVA-env, MVA-gag-pol-env, or MVA. Plasma viral load was determined by real-time RT-PCR as described in Materials and Methods. Results are expressed as number of copies of SIV genomic RNA equivalent per milliliter of plasma. Plasma samples having values under assay threshold sensitivity were given a value of 800 copy eq/ml. Animals sacrificed because of clinical manifestations of AIDS () and the animal that died of causes unrelated to AIDS (✞) are labeled.

  • Fig. 6.
    • Open in new tab
    • Download powerpoint
    Fig. 6.

    Geometric means of plasma viral load values for groups of immunized and control macaques after challenge with uncloned SIVsmE660. Significant reductions in geometric mean plasma viral load were observed in macaques immunized prior to SIV challenge with recombinant MVA expressing SIVsmH-4 proteins Gag-Pol, Env, or Gag-Pol-Env as compared to those immunized with nonrecombinant MVA (repeated measures ANOVA, P = 0.0011). The error bars represent the standard errors of the means of duplicated measurements for six macaques in each group.

  • Fig. 7.
    • Open in new tab
    • Download powerpoint
    Fig. 7.

    Peripheral blood CD4+ T-lymphocyte levels in immunized and control macaques infected with uncloned SIVsmE660. Sequential levels of peripheral CD4+ T cells over the first 45 weeks after SIV challenge are shown for animals immunized prior to challenge with MVA-gag-pol, MVA-env, MVA-gag-pol-env, or MVA. Animals sacrificed because of clinical manifestations of AIDS () and the animal that died of causes unrelated to AIDS (✞) are labeled. CD4+ T-lymphocyte levels were evaluated by fluorescence-activated cell sorting on whole heparinized blood samples using methods previously described (33).

  • Fig. 8.
    • Open in new tab
    • Download powerpoint
    Fig. 8.

    Survival rates for immunized and control macaques. Kaplan-Meier plot of cumulative survival rates in the first 590 days after challenge indicates significant differences between MVA-immunized- and MVA-SIV-immunized macaques.

Tables

  • Figures
  • Table 1.

    Production of SIV RT and CA protein in culture media of BS-C-1 cells infected with MVA-SIV recombinant virusesa

    MVA recombinantRT activity (103cpm)bCA antigen (ng/ml)b
    MVA-SIV (Original)54 ± 616 ± 1
    MVA-gag-pol-env 1,683 ± 27870 ± 12
    MVA-gag-pol 1,706 ± 92870 ± 12
    • ↵a BS-C-1 cells were infected with 10 PFU of indicated MVA-SIV recombinant per cell, and samples were collected as described in Materials and Methods.

    • ↵b Results are normalized to 106infected cells and are presented as average values of three independent experiments ± standard derivations.

  • Table 2.

    Neutralizing antibody titers to the vaccine (SIVsmH-4) and challenge (SIVsmE660) viruses on the day of challenge

    VaccineMacaque no.Reciprocal neutralizing dilution titer for:
    SIVsmH-4SIVsmE660
    MVA-env B1<30<30
    B2286<30
    B3<30<30
    B4<30<30
    B5<30<30
    B686<30
    MVA-gag-pol-env C1274<30
    C2<30<30
    C3<30<30
    C4107<30
    C585<30
    C688<30
  • Table 3.

    Summary of virus isolation results from PBMC of MVA-immunized macaques

    ImmunogenMacaqueWeek post-SIV Inoculation
    123468121620283644
    MVA-gag-pol A1++++−−−−−−−−
    A2++++++++++++
    A3+++−−++−−−−−
    A4++++++++++++
    A5++++++++++++
    A6++++++++++++
    MVA-env B1++++−++−−−−−
    B2++++++++++++
    B3++++++++++++
    B4++++++++++++
    B5++++++++++++
    B6++++++++++++
    MVA-gag-pol-env C1++++++++++++
    C2++++++++++++
    C3++++++++++++
    C4++++++−−−−−−
    C5++++++++++++
    C6++++++++++++
    MVAD1++++++++++++
    D2++++++++++Dead
    D3+++++++++Dead
    D4+++++++++++Dead
    D5++++++++Dead
    D6++++++++++++
PreviousNext
Back to top
Download PDF
Citation Tools
Comparative Efficacy of Recombinant Modified Vaccinia Virus Ankara Expressing Simian Immunodeficiency Virus (SIV) Gag-Pol and/or Env in Macaques Challenged with Pathogenic SIV
Ilnour Ourmanov, Charles R. Brown, Bernard Moss, Miles Carroll, Linda Wyatt, Liuobov Pletneva, Simoy Goldstein, David Venzon, Vanessa M. Hirsch
Journal of Virology Mar 2000, 74 (6) 2740-2751; DOI: 10.1128/JVI.74.6.2740-2751.2000

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Print

Alerts
Sign In to Email Alerts with your Email Address
Email

Thank you for sharing this Journal of Virology article.

NOTE: We request your email address only to inform the recipient that it was you who recommended this article, and that it is not junk mail. We do not retain these email addresses.

Enter multiple addresses on separate lines or separate them with commas.
Comparative Efficacy of Recombinant Modified Vaccinia Virus Ankara Expressing Simian Immunodeficiency Virus (SIV) Gag-Pol and/or Env in Macaques Challenged with Pathogenic SIV
(Your Name) has forwarded a page to you from Journal of Virology
(Your Name) thought you would be interested in this article in Journal of Virology.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
Comparative Efficacy of Recombinant Modified Vaccinia Virus Ankara Expressing Simian Immunodeficiency Virus (SIV) Gag-Pol and/or Env in Macaques Challenged with Pathogenic SIV
Ilnour Ourmanov, Charles R. Brown, Bernard Moss, Miles Carroll, Linda Wyatt, Liuobov Pletneva, Simoy Goldstein, David Venzon, Vanessa M. Hirsch
Journal of Virology Mar 2000, 74 (6) 2740-2751; DOI: 10.1128/JVI.74.6.2740-2751.2000
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
  • Top
  • Article
    • ABSTRACT
    • MATERIALS AND METHODS
    • RESULTS
    • DISCUSSION
    • ACKNOWLEDGMENTS
    • FOOTNOTES
    • REFERENCES
  • Figures & Data
  • Info & Metrics
  • PDF

KEYWORDS

Fusion Proteins, gag-pol
Gene Products, env
Membrane Glycoproteins
SAIDS Vaccines
Simian Acquired Immunodeficiency Syndrome
simian immunodeficiency virus
Vaccines, DNA
vaccinia virus
Viral Envelope Proteins

Related Articles

Cited By...

About

  • About JVI
  • Editor in Chief
  • Editorial Board
  • Policies
  • For Reviewers
  • For the Media
  • For Librarians
  • For Advertisers
  • Alerts
  • RSS
  • FAQ
  • Permissions
  • Journal Announcements

Authors

  • ASM Author Center
  • Submit a Manuscript
  • Article Types
  • Ethics
  • Contact Us

Follow #Jvirology

@ASMicrobiology

       

 

JVI in collaboration with

American Society for Virology

ASM Journals

ASM journals are the most prominent publications in the field, delivering up-to-date and authoritative coverage of both basic and clinical microbiology.

About ASM | Contact Us | Press Room

 

ASM is a member of

Scientific Society Publisher Alliance

 

American Society for Microbiology
1752 N St. NW
Washington, DC 20036
Phone: (202) 737-3600

Copyright © 2021 American Society for Microbiology | Privacy Policy | Website feedback

Print ISSN: 0022-538X; Online ISSN: 1098-5514