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
Pathogenesis and Immunity

Broad Neutralization of Human Immunodeficiency Virus Type 1 Mediated by Plasma Antibodies against the gp41 Membrane Proximal External Region

Elin S. Gray, Maphuti C. Madiga, Penny L. Moore, Koleka Mlisana, Salim S. Abdool Karim, James M. Binley, George M. Shaw, John R. Mascola, Lynn Morris
Elin S. Gray
1AIDS Virus Research Unit, National Institute for Communicable Diseases, Johannesburg, South Africa
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Maphuti C. Madiga
1AIDS Virus Research Unit, National Institute for Communicable Diseases, Johannesburg, South Africa
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Penny L. Moore
1AIDS Virus Research Unit, National Institute for Communicable Diseases, Johannesburg, South Africa
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Koleka Mlisana
2Centre for the AIDS Programme of Research in South Africa (CAPRISA), University of KwaZulu Natal, Durban, South Africa
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Salim S. Abdool Karim
2Centre for the AIDS Programme of Research in South Africa (CAPRISA), University of KwaZulu Natal, Durban, South Africa
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
James M. Binley
3Torrey Pines Institute for Molecular Studies, San Diego, California 92121
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
George M. Shaw
4University of Alabama at Birmingham, Birmingham, Alabama 35294
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
John R. Mascola
5Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Lynn Morris
1AIDS Virus Research Unit, National Institute for Communicable Diseases, Johannesburg, South Africa
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: lynnm@nicd.ac.za
DOI: 10.1128/JVI.01359-09
  • Article
  • Figures & Data
  • Info & Metrics
  • PDF
Loading

Article Figures & Data

Figures

  • Tables
  • Additional Files
  • FIG. 1.
    • Open in new tab
    • Download powerpoint
    FIG. 1.

    Adsorption of anti-MPER antibodies from plasmas BB34, BB81, and BB105. MAb 4E10 and plasma samples were adsorbed with MPER-peptide-coated beads or blank beads or left untreated. (A) All samples were assayed by ELISA for binding to the MPER or V3 peptide and tested for neutralization of the HIV-2-HIV-1 MPER chimera C1C. OD, optical density; conc, concentration. (B) Adsorbed plasmas were tested for neutralization of the HIV-1 envelope-pseudotyped viruses COT6.15, CAP206.8, and Du156.12.

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

    Antibodies eluted from MPER-coated beads contain cross-neutralizing activity. (A) Neutralization of C1C by eluates from MPER-coated beads of plasmas BB34, CAP206, and SAC21 and MAbs 4E10, Z13e1, and 2F5. conc, concentration. (B) Neutralization of HIV-1 subtype C envelope-pseudotyped viruses COT6.15, ZM197M.PB7, Du156.12, and CAP206.8 and subtype B TRO.11 and JR-FL.

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

    Comparison of the IgG subclass profiles between original plasmas and eluates from MPER-coated beads. The pie charts represent the IgG subclasses found in the BB34, CAP206, and SAC21 plasmas and eluates. The table shows the IgG subclass concentrations in plasmas and in eluates. b.d, below detection level.

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

    Neutralizing anti-MPER antibodies are IgG3 in BB34 but not in CAP206. (A and B) IgG subclass profiles of total IgG, FTpA, and EpA of BB34 (A) and CAP206 (B). (C) BB34 fractions were tested for neutralization of C1C and HIV-1 envelope-pseudotyped viruses, as well as binding to the MPER peptide in ELISA. OD, optical density; conc, concentration. (D) CAP206 fractions were tested for neutralization of C1C and HIV-1 envelope-pseudotyped viruses.

Tables

  • Figures
  • Additional Files
  • TABLE 1.

    Screening for broadly cross-neutralizing plasma samples containing anti-MPER antibodies

    ParameteraValue in:
    BB cohortCAPRISASAC cohort
    Total no. of plasmas701868
    No. (%) BCN16 (23)b4 (22)c17 (25)d
    No. of BCN anti-MPER antibodies positive1126
    No. of BCN anti-MPER titers > 1:1,000114
    No. MPER peptide binding111
    Sample analyzedBB34CAP206SAC21
    • ↵ a BCN, broadly cross-neutralizing. Anti-MPER activity was defined as neutralization of the HIV-2-HIV-1 MPER chimeric virus C1C.

    • ↵ b BCN plasmas were defined as able to neutralize at least 8 of 10 viruses tested (12).

    • ↵ c BCN plasmas were defined as able to neutralize at least 8 of 12 viruses from the tier 2 subtype C virus panel.

    • ↵ d BCN plasmas were defined as able to neutralize at least four of six viruses tested.

  • TABLE 2.

    Effect of anti-MPER antibody adsorbtions on neutralization breadth

    SubtypeVirusID50% Reductionc
    BlankaMPERb
    Adsorbed BB34 plasma
        HIV-2/HIV-1 MPERC1C4,80241 99
        Subtype CCOT6.151,35065 95
    CAP85 97,1341,140 84
    CAP88 B5258<40 84
    CAP206 81,35086 94
    CAP210 B814810231
    CAP228 5124573 70
    CAP255 16164<40 76
    Du151.24846360
    Du422.1155<40 74
    Du156.123,869151 96
    ZM197M.PB71,068<40 96
    ZM233M.PB621966 70
    ZM135M.PL10a1,651250 85
        Subtype B6535.3549102 81
    QHO692.4217942 77
    CAAN5342.A21391297
    TRO.11646<40 94
    SC422661.8758175 77
    REJO4541.6733180 76
    JR-FL129<40 69
        Subtype A92RW0091,29682732
        Subtype D92UG0241,4801,00632
    Adsorbed CAP206 plasma
        HIV-2/HIV-1 MPERC1C4,527222 95
        Subtype CCOT6.151,236109 91
    CAP45 G34,720193 96
    CAP63 A918013227
    CAP85 92,856352 88
    CAP88 B5223<40 82
    CAP206 81,8701,55517
    Du151.2105<40 62
    Du422.116547 72
    Du156.1269257 92
    Du172.17234<40 83
    ZM197M.PB730982 73
    ZM135M.PL10a24891 63
        Subtype BQHO692.4238366 83
    AC10.0.2911147 58
    WITO4160.331449931
    TRO.11491<40 92
        Subtype A92RW00991579313
    Q23.173203400
        Subtype D92UG0241,5561,26819
    Adsorbed SAC21 plasma
        HIV-2/HIV-1 MPERC1C3,157246 92
        Subtype CCOT6.15183<40 78
    CAP85 944727638
    CAP88 B58842 52
    CAP206 8361140 61
    CAP255 161091150
    Du151.21176941
    ZM197M.PB71178527
    ZM233M.PB61007921
    ZM135M.PL10a1,114301 73
        Subtype BTRO.1114747 68
    SC422661.888<40 55
        Subtype A92RW0091,6651,04537
        Subtype D92UG0241,8891,49121
    • ↵ a ID50 of plasmas adsorbed on blank beads. These titers were similar to the ID50 obtained with the untreated sera.

    • ↵ b ID50 of plasmas adsorbed on beads coated with the MPER peptide.

    • ↵ c Percentage reduction in ID50 due to adsorption on MPER-coated beads (1 − MPER/blank). Cases where the percent reduction was >50% are in boldface.

  • TABLE 3.

    Mapping of anti-MPER neutralizing antibodies

    ChimeraMPER sequenceaNeutralizationbPlasma ID50
    2F54E10Z13e1BB34CAP206SAC21
    7312A NMYEL660QKLNSWDVFG670NWFDLASWVK680YIQYGVYIV −−−<2021<20
    C1 NMYEL660LALDKWASLW670NWFDITKWLW680YIKYGVYIV ++++++5,5603,9033,871
    C1C NMYEL660LALDSWKNLW670NWFDITKWLW680YIKYGVYIV −++++3,9452,8672,733
    C1C F/L NMYEL660LALDSWKNLW670NWLDITKWLW680YIKYGVYIV −−+1,7792,4491,802
    C3 NMYEL660LALDKWASLW670NWFDLASWVK680YIQYGVYIV ++−−<20<20<20
    C7(2F5) NMYEL660QALDKWAVFG670NWFDLASWVK680YIQYGVYIV ++−−<20<20<20
    C6(4E10) NMYEL660QKLNSWDVFG670NWFDITSWIK680YIQYGVYIV −++−<20<20<20
    C4 NMYEL660QKLNSWDVFG670NWFDITKWLW680YIKYGVYIV −+++/−<20723189
    C4GW NMYEL660QKLNSWDVFW670NWFDITKWLW680YIKYGVYIV −++++7,4823,0672,987
    C8 NMYEL660QKLNSWDSLW670NWFDITKWLW680YIKYGVYIV −+++3,3512,5381,199
    • ↵ a Grafted amino acids are indicated in italics, with the 7312A residues in lightface. Further mutations on the chimeras are in boldface.

    • ↵ b Neutralization by MAbs 2F5, 4E10, and Z13e1 are qualitatively indicated relative to the titers obtained with the C1 chimera. −, no neutralization; ++, neutralization similar to that of C1; +, neutralization within 3-fold of that of C1; +/−, neutralization within 10-fold of that of C1.

  • TABLE 4.

    Relative neutralization of pseudotyped COT6.15 envelope MPER mutantsa

    COT6.154E10BB34CAP206SAC21
    IC50RatiobID50RatiocID50RatiocID50Ratioc
    Wild type0.91.01,3921.01,2561.03171.0
    A662G0.120.14,8990.32,4430.59780.3
    L663A0.020.08,7140.27,9710.25,6600.1
    D664A0.770.91,1491.28441.52381.3
    S665A0.140.25,4950.31,5620.81,7870.2
    W666A0.510.65,5540.34,2940.34460.7
    K667A0.050.13,2610.41,6940.71,7340.2
    N668A1.31.48311.74253.02081.5
    L669A0.050.13,8470.43,1380.41,1950.3
    W670A0.110.1 132 10.5 1,0541.2 105 3.0
    S671A0.040.03,1020.41,6140.89280.3
    W672A >25 >25 2,9590.52,2440.64680.7
    F673A >25 >25 7791.84982.5 <50 >6.3
    D674A1.41.6 <50 >25 <50 >25 <50 >6.3
    D674S2.492.8 <50 >25 90 14.0 <50 >6.3
    D674N0.330.46632.16432.01492.1
    I675A0.040.04,0690.32,0650.67180.4
    T676A 21.77 24.2 2,3800.68951.45240.6
    K677A0.050.14,6710.32,1510.611540.3
    W678A0.050.13,8420.41,8850.71,0070.3
    L679A0.090.12,0850.71,4480.92251.4
    W680A 10.89 12.1 7311.99041.41422.2
    • ↵ a Cases with more than a 3-fold drop in the ID50 or IC50 are in boldface.

    • ↵ b (Mutant IC50)/(wild-type IC50) ratio.

    • ↵ c (Wild-type ID50)/(mutant ID50) ratio.

Additional Files

  • Figures
  • Tables
  • Supplemental material

    Files in this Data Supplement:

    • Supplemental file 1 - Fig. S1 (MPER sequences of the viruses used in this study.)
      Table S1 (Neutralizing activity of the three plasmas used in this study.)
      MS PowerPoint file, 72K.
PreviousNext
Back to top
Download PDF
Citation Tools
Broad Neutralization of Human Immunodeficiency Virus Type 1 Mediated by Plasma Antibodies against the gp41 Membrane Proximal External Region
Elin S. Gray, Maphuti C. Madiga, Penny L. Moore, Koleka Mlisana, Salim S. Abdool Karim, James M. Binley, George M. Shaw, John R. Mascola, Lynn Morris
Journal of Virology Oct 2009, 83 (21) 11265-11274; DOI: 10.1128/JVI.01359-09

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.
Broad Neutralization of Human Immunodeficiency Virus Type 1 Mediated by Plasma Antibodies against the gp41 Membrane Proximal External Region
(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
Broad Neutralization of Human Immunodeficiency Virus Type 1 Mediated by Plasma Antibodies against the gp41 Membrane Proximal External Region
Elin S. Gray, Maphuti C. Madiga, Penny L. Moore, Koleka Mlisana, Salim S. Abdool Karim, James M. Binley, George M. Shaw, John R. Mascola, Lynn Morris
Journal of Virology Oct 2009, 83 (21) 11265-11274; DOI: 10.1128/JVI.01359-09
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

antibodies
HIV Envelope Protein gp41
HIV-1

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