IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v13y2022i1d10.1038_s41467-022-28250-7.html
   My bibliography  Save this article

Phagocytosis by an HIV antibody is associated with reduced viremia irrespective of enhanced complement lysis

Author

Listed:
  • David A. Spencer

    (Oregon National Primate Research Center, Oregon Health & Science University
    Absci Corp)

  • Benjamin S. Goldberg

    (Dartmouth College)

  • Shilpi Pandey

    (Oregon National Primate Research Center, Oregon Health & Science University)

  • Tracy Ordonez

    (Oregon National Primate Research Center, Oregon Health & Science University)

  • Jérémy Dufloo

    (Institut Pasteur
    University of Valencia-CSIC)

  • Philip Barnette

    (Oregon National Primate Research Center, Oregon Health & Science University)

  • William F. Sutton

    (Oregon National Primate Research Center, Oregon Health & Science University)

  • Heidi Henderson

    (Oregon National Primate Research Center, Oregon Health & Science University)

  • Rebecca Agnor

    (Oregon Health & Science University)

  • Lina Gao

    (Oregon Health & Science University)

  • Timothée Bruel

    (Institut Pasteur
    Vaccine Research Institute)

  • Olivier Schwartz

    (Institut Pasteur
    Vaccine Research Institute)

  • Nancy L. Haigwood

    (Oregon National Primate Research Center, Oregon Health & Science University
    Oregon Health & Science University)

  • Margaret E. Ackerman

    (Dartmouth College)

  • Ann J. Hessell

    (Oregon National Primate Research Center, Oregon Health & Science University)

Abstract

Increasingly, antibodies are being used to treat and prevent viral infections. In the context of HIV, efficacy is primarily attributed to dose-dependent neutralization potency and to a lesser extent Fc-mediated effector functions. It remains unclear whether augmenting effector functions of broadly neutralizing antibodies (bNAbs) may improve their clinical potential. Here, we use bNAb 10E8v4 targeting the membrane external proximal region (MPER) to examine the role of antibody-mediated effector and complement (C’) activity when administered prophylactically against SHIV challenge in rhesus macaques. With sub-protective dosing, we find a 78–88% reduction in post-acute viremia that is associated with 10E8v4-mediated phagocytosis acting at the time of challenge. Neither plasma nor tissue viremic outcomes in vivo is improved with an Fc-modified variant of 10E8v4 enhanced for C’ functions as determined in vitro. These results suggest that effector functions inherent to unmodified 10E8v4 contribute to efficacy against SHIVSF162P3 in the absence of plasma neutralizing titers, while C’ functions are dispensable in this setting, informing design of bNAb modifications for improving protective efficacy.

Suggested Citation

  • David A. Spencer & Benjamin S. Goldberg & Shilpi Pandey & Tracy Ordonez & Jérémy Dufloo & Philip Barnette & William F. Sutton & Heidi Henderson & Rebecca Agnor & Lina Gao & Timothée Bruel & Olivier Sc, 2022. "Phagocytosis by an HIV antibody is associated with reduced viremia irrespective of enhanced complement lysis," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
  • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-28250-7
    DOI: 10.1038/s41467-022-28250-7
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-022-28250-7
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-022-28250-7?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Ping Zhu & Jun Liu & Julian Bess & Elena Chertova & Jeffrey D. Lifson & Henry Grisé & Gilad A. Ofek & Kenneth A. Taylor & Kenneth H. Roux, 2006. "Distribution and three-dimensional structure of AIDS virus envelope spikes," Nature, Nature, vol. 441(7095), pages 847-852, June.
    2. Ann J. Hessell & Lars Hangartner & Meredith Hunter & Carin E. G. Havenith & Frank J. Beurskens & Joost M. Bakker & Caroline M. S. Lanigan & Gary Landucci & Donald N. Forthal & Paul W. H. I. Parren & P, 2007. "Fc receptor but not complement binding is important in antibody protection against HIV," Nature, Nature, vol. 449(7158), pages 101-104, September.
    3. Xiping Wei & Julie M. Decker & Shuyi Wang & Huxiong Hui & John C. Kappes & Xiaoyun Wu & Jesus F. Salazar-Gonzalez & Maria G. Salazar & J. Michael Kilby & Michael S. Saag & Natalia L. Komarova & Martin, 2003. "Antibody neutralization and escape by HIV-1," Nature, Nature, vol. 422(6929), pages 307-312, March.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Kun-Wei Chan & Christina C. Luo & Hong Lu & Xueling Wu & Xiang-Peng Kong, 2021. "A site of vulnerability at V3 crown defined by HIV-1 bNAb M4008_N1," Nature Communications, Nature, vol. 12(1), pages 1-12, December.
    2. Shuang Yang & Giorgos Hiotis & Yi Wang & Junjian Chen & Jia-huai Wang & Mikyung Kim & Ellis L. Reinherz & Thomas Walz, 2022. "Dynamic HIV-1 spike motion creates vulnerability for its membrane-bound tripod to antibody attack," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    3. Kemin Tan & Junjian Chen & Yu Kaku & Yi Wang & Luke Donius & Rafiq Ahmad Khan & Xiaolong Li & Hannah Richter & Michael S. Seaman & Thomas Walz & Wonmuk Hwang & Ellis L. Reinherz & Mikyung Kim, 2023. "Inadequate structural constraint on Fab approach rather than paratope elicitation limits HIV-1 MPER vaccine utility," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    4. Karunasinee Suphaphiphat & Delphine Desjardins & Valérie Lorin & Nastasia Dimant & Kawthar Bouchemal & Laetitia Bossevot & Maxence Galpin-Lebreau & Nathalie Dereuddre-Bosquet & Hugo Mouquet & Roger Gr, 2023. "Mucosal application of the broadly neutralizing antibody 10-1074 protects macaques from cell-associated SHIV vaginal exposure," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    5. Zhentao Sang & Lu Xu & Renyu Ding & Minjun Wang & Xiaoran Yang & Xitan Li & Bingxin Zhou & Kaijun Gou & Yang Han & Tingting Liu & Xuchun Chen & Ying Cheng & Huazhe Yang & Heran Li, 2023. "Nanoparticles exhibiting virus-mimic surface topology for enhanced oral delivery," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    6. Carsten Magnus & Roland R Regoes, 2010. "Estimating the Stoichiometry of HIV Neutralization," PLOS Computational Biology, Public Library of Science, vol. 6(3), pages 1-11, March.
    7. Yi-Nan Zhang & Jennifer Paynter & Aleksandar Antanasijevic & Joel D. Allen & Mor Eldad & Yi-Zong Lee & Jeffrey Copps & Maddy L. Newby & Linling He & Deborah Chavez & Pat Frost & Anna Goodroe & John Du, 2023. "Single-component multilayered self-assembling protein nanoparticles presenting glycan-trimmed uncleaved prefusion optimized envelope trimers as HIV-1 vaccine candidates," Nature Communications, Nature, vol. 14(1), pages 1-29, December.
    8. Olivier Lambotte & Justin Pollara & Faroudy Boufassa & Christiane Moog & Alain Venet & Barton F Haynes & Jean-François Delfraissy & Asier Saez-Cirion & Guido Ferrari, 2013. "High Antibody-Dependent Cellular Cytotoxicity Responses Are Correlated with Strong CD8 T Cell Viral Suppressive Activity but Not with B57 Status in HIV-1 Elite Controllers," PLOS ONE, Public Library of Science, vol. 8(9), pages 1-5, September.
    9. Jeffrey E. Harris, 2021. "The Repeated Setbacks of HIV Vaccine Development Laid the Groundwork for SARS-CoV-2 Vaccines," NBER Working Papers 28587, National Bureau of Economic Research, Inc.
    10. Joana Dias & Giulia Fabozzi & Slim Fourati & Xuejun Chen & Cuiping Liu & David R. Ambrozak & Amy Ransier & Farida Laboune & Jianfei Hu & Wei Shi & Kylie March & Anna A. Maximova & Stephen D. Schmidt &, 2024. "Administration of anti-HIV-1 broadly neutralizing monoclonal antibodies with increased affinity to Fcγ receptors during acute SHIVAD8-EO infection," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    11. Lucia Reh & Carsten Magnus & Merle Schanz & Jacqueline Weber & Therese Uhr & Peter Rusert & Alexandra Trkola, 2015. "Capacity of Broadly Neutralizing Antibodies to Inhibit HIV-1 Cell-Cell Transmission Is Strain- and Epitope-Dependent," PLOS Pathogens, Public Library of Science, vol. 11(7), pages 1-34, July.
    12. Wayne Delport & Konrad Scheffler & Cathal Seoighe, 2008. "Frequent Toggling between Alternative Amino Acids Is Driven by Selection in HIV-1," PLOS Pathogens, Public Library of Science, vol. 4(12), pages 1-13, December.
    13. Terrence M Dobrowsky & Brian R Daniels & Robert F Siliciano & Sean X Sun & Denis Wirtz, 2010. "Organization of Cellular Receptors into a Nanoscale Junction during HIV-1 Adhesion," PLOS Computational Biology, Public Library of Science, vol. 6(7), pages 1-14, July.
    14. Shixia Wang & Kun-Wei Chan & Danlan Wei & Xiuwen Ma & Shuying Liu & Guangnan Hu & Saeyoung Park & Ruimin Pan & Ying Gu & Alexandra F. Nazzari & Adam S. Olia & Kai Xu & Bob C. Lin & Mark K. Louder & Kr, 2024. "Human CD4-binding site antibody elicited by polyvalent DNA prime-protein boost vaccine neutralizes cross-clade tier-2-HIV strains," Nature Communications, Nature, vol. 15(1), pages 1-13, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-28250-7. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.