IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v14y2023i1d10.1038_s41467-023-40918-2.html
   My bibliography  Save this article

Engaging an HIV vaccine target through the acquisition of low B cell affinity

Author

Listed:
  • Larance Ronsard

    (The Massachusetts Institute of Technology and Harvard University)

  • Ashraf S. Yousif

    (The Massachusetts Institute of Technology and Harvard University)

  • Faez Amokrane Nait Mohamed

    (The Massachusetts Institute of Technology and Harvard University)

  • Jared Feldman

    (The Massachusetts Institute of Technology and Harvard University)

  • Vintus Okonkwo

    (The Massachusetts Institute of Technology and Harvard University)

  • Caitlin McCarthy

    (The Massachusetts Institute of Technology and Harvard University)

  • Julia Schnabel

    (The Massachusetts Institute of Technology and Harvard University)

  • Timothy Caradonna

    (The Massachusetts Institute of Technology and Harvard University)

  • Ralston M. Barnes

    (Bristol-Myers Squibb)

  • Daniel Rohrer

    (Bristol-Myers Squibb)

  • Nils Lonberg

    (Bristol-Myers Squibb)

  • Aaron Schmidt

    (The Massachusetts Institute of Technology and Harvard University
    Harvard Medical School)

  • Daniel Lingwood

    (The Massachusetts Institute of Technology and Harvard University)

Abstract

Low affinity is common for germline B cell receptors (BCR) seeding development of broadly neutralizing antibodies (bnAbs) that engage hypervariable viruses, including HIV. Antibody affinity selection is also non-homogenizing, insuring the survival of low affinity B cell clones. To explore whether this provides a natural window for expanding human B cell lineages against conserved vaccine targets, we deploy transgenic mice mimicking human antibody diversity and somatic hypermutation (SHM) and immunize with simple monomeric HIV glycoprotein envelope immunogens. We report an immunization regimen that focuses B cell memory upon the conserved CD4 binding site (CD4bs) through both conventional affinity maturation and reproducible expansion of low affinity BCR clones with public patterns in SHM. In the latter instance, SHM facilitates target acquisition by decreasing binding strength. This suggests that permissive B cell selection enables the discovery of antibody epitopes, in this case an HIV bnAb site.

Suggested Citation

  • Larance Ronsard & Ashraf S. Yousif & Faez Amokrane Nait Mohamed & Jared Feldman & Vintus Okonkwo & Caitlin McCarthy & Julia Schnabel & Timothy Caradonna & Ralston M. Barnes & Daniel Rohrer & Nils Lonb, 2023. "Engaging an HIV vaccine target through the acquisition of low B cell affinity," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
  • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-40918-2
    DOI: 10.1038/s41467-023-40918-2
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-023-40918-2
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-023-40918-2?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. Jeong Hyun Lee & Henry J. Sutton & Christopher A. Cottrell & Ivy Phung & Gabriel Ozorowski & Leigh M. Sewall & Rebecca Nedellec & Catherine Nakao & Murillo Silva & Sara T. Richey & Jonathan L. Torres , 2022. "Long-primed germinal centres with enduring affinity maturation and clonal migration," Nature, Nature, vol. 609(7929), pages 998-1004, September.
    2. Daniel Lingwood & Patrick M. McTamney & Hadi M. Yassine & James R. R. Whittle & Xiaoti Guo & Jeffrey C. Boyington & Chih-Jen Wei & Gary J. Nabel, 2012. "Structural and genetic basis for development of broadly neutralizing influenza antibodies," Nature, Nature, vol. 489(7417), pages 566-570, September.
    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. Brian M. Petersen & Monica B. Kirby & Karson M. Chrispens & Olivia M. Irvin & Isabell K. Strawn & Cyrus M. Haas & Alexis M. Walker & Zachary T. Baumer & Sophia A. Ulmer & Edgardo Ayala & Emily R. Rhod, 2024. "An integrated technology for quantitative wide mutational scanning of human antibody Fab libraries," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    2. Ivy Phung & Kristen A. Rodrigues & Ester Marina-Zárate & Laura Maiorino & Bapi Pahar & Wen-Hsin Lee & Mariane Melo & Amitinder Kaur & Carolina Allers & Marissa Fahlberg & Brooke F. Grasperge & Jason P, 2023. "A combined adjuvant approach primes robust germinal center responses and humoral immunity in non-human primates," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    3. Ivan V. Kuzmin & Ruben Soto Acosta & Layne Pruitt & Perry T. Wasdin & Kritika Kedarinath & Keziah R. Hernandez & Kristyn A. Gonzales & Kharighan Hill & Nicole G. Weidner & Chad Mire & Taylor B. Engdah, 2024. "Comparison of uridine and N1-methylpseudouridine mRNA platforms in development of an Andes virus vaccine," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    4. Annemart Koornneef & Kanika Vanshylla & Gijs Hardenberg & Lucy Rutten & Nika M. Strokappe & Jeroen Tolboom & Jessica Vreugdenhil & Karin Feddes-de Boer & Aditya Perkasa & Sven Blokland & Judith A. Bur, 2024. "CoPoP liposomes displaying stabilized clade C HIV-1 Env elicit tier 2 multiclade neutralization in rabbits," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    5. Fabian Sesterhenn & Che Yang & Jaume Bonet & Johannes T. Cramer & Xiaolin Wen & Yimeng Wang & Chi I. Chiang & Luciano Andres Abriata & Iga Kucharska & Giacomo Castoro & Sabrina S. Vollers & Marie Gall, 2020. "De novo protein design enables the precise induction of RSV-neutralizing antibodies," Post-Print hal-02677103, HAL.
    6. Eike-Christian Wamhoff & Larance Ronsard & Jared Feldman & Grant A. Knappe & Blake M. Hauser & Anna Romanov & James Brett Case & Shilpa Sanapala & Evan C. Lam & Kerri J. St. Denis & Julie Boucau & Amy, 2024. "Enhancing antibody responses by multivalent antigen display on thymus-independent DNA origami scaffolds," 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:14:y:2023:i:1:d:10.1038_s41467-023-40918-2. 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.