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A combined adjuvant approach primes robust germinal center responses and humoral immunity in non-human primates

Author

Listed:
  • Ivy Phung

    (La Jolla Institute for Immunology (LJI)
    The Scripps Research Institute
    University of California, San Diego (UCSD))

  • Kristen A. Rodrigues

    (Massachusetts Institute of Technology
    Massachusetts Institute of Technology and Harvard University)

  • Ester Marina-Zárate

    (La Jolla Institute for Immunology (LJI)
    The Scripps Research Institute)

  • Laura Maiorino

    (Massachusetts Institute of Technology
    Massachusetts Institute of Technology and Harvard University)

  • Bapi Pahar

    (Tulane School of Medicine)

  • Wen-Hsin Lee

    (The Scripps Research Institute)

  • Mariane Melo

    (The Scripps Research Institute
    Massachusetts Institute of Technology
    Massachusetts Institute of Technology and Harvard University)

  • Amitinder Kaur

    (Tulane School of Medicine)

  • Carolina Allers

    (Tulane School of Medicine)

  • Marissa Fahlberg

    (Tulane School of Medicine)

  • Brooke F. Grasperge

    (Tulane School of Medicine)

  • Jason P. Dufour

    (Tulane School of Medicine)

  • Faith Schiro

    (Tulane School of Medicine)

  • Pyone P. Aye

    (Tulane School of Medicine)

  • Paul G. Lopez

    (La Jolla Institute for Immunology (LJI))

  • Jonathan L. Torres

    (The Scripps Research Institute)

  • Gabriel Ozorowski

    (The Scripps Research Institute
    The Scripps Research Institute
    The Scripps Research Institute)

  • Saman Eskandarzadeh

    (The Scripps Research Institute
    The Scripps Research Institute
    The Scripps Research Institute)

  • Michael Kubitz

    (The Scripps Research Institute
    The Scripps Research Institute
    The Scripps Research Institute)

  • Erik Georgeson

    (The Scripps Research Institute
    The Scripps Research Institute
    The Scripps Research Institute)

  • Bettina Groschel

    (The Scripps Research Institute
    The Scripps Research Institute
    The Scripps Research Institute)

  • Rebecca Nedellec

    (The Scripps Research Institute)

  • Michael Bick

    (The Scripps Research Institute)

  • Katarzyna Kaczmarek Michaels

    (Massachusetts Institute of Technology
    Massachusetts Institute of Technology and Harvard University)

  • Hongmei Gao

    (Duke University Medical Center, Duke University)

  • Xiaoying Shen

    (Duke University Medical Center, Duke University)

  • Diane G. Carnathan

    (Emory University School of Medicine)

  • Guido Silvestri

    (Emory University School of Medicine)

  • David C. Montefiori

    (Duke University Medical Center, Duke University)

  • Andrew B. Ward

    (The Scripps Research Institute
    The Scripps Research Institute)

  • Lars Hangartner

    (The Scripps Research Institute
    The Scripps Research Institute)

  • Ronald S. Veazey

    (Tulane School of Medicine)

  • Dennis R. Burton

    (The Scripps Research Institute
    Massachusetts Institute of Technology and Harvard University
    The Scripps Research Institute
    The Scripps Research Institute)

  • William R. Schief

    (The Scripps Research Institute
    Massachusetts Institute of Technology and Harvard University
    The Scripps Research Institute
    The Scripps Research Institute)

  • Darrell J. Irvine

    (The Scripps Research Institute
    Massachusetts Institute of Technology
    Massachusetts Institute of Technology and Harvard University
    Massachusetts Institute of Technology)

  • Shane Crotty

    (La Jolla Institute for Immunology (LJI)
    The Scripps Research Institute
    University of California, San Diego (UCSD))

Abstract

Adjuvants and antigen delivery kinetics can profoundly influence B cell responses and should be critically considered in rational vaccine design, particularly for difficult neutralizing antibody targets such as human immunodeficiency virus (HIV). Antigen kinetics can change depending on the delivery method. To promote extended immunogen bioavailability and to present antigen in a multivalent form, native-HIV Env trimers are modified with short phosphoserine peptide linkers that promote tight binding to aluminum hydroxide (pSer:alum). Here we explore the use of a combined adjuvant approach that incorporates pSer:alum-mediated antigen delivery with potent adjuvants (SMNP, 3M-052) in an extensive head-to-head comparison study with conventional alum to assess germinal center (GC) and humoral immune responses. Priming with pSer:alum plus SMNP induces additive effects that enhance the magnitude and persistence of GCs, which correlate with better GC-TFH cell help. Autologous HIV-neutralizing antibody titers are improved in SMNP-immunized animals after two immunizations. Over 9 months after priming immunization of pSer:alum with either SMNP or 3M-052, robust Env-specific bone marrow plasma cells (BM BPC) are observed. Furthermore, pSer-modification of Env trimer reduce targeting towards immunodominant non-neutralizing epitopes. The study shows that a combined adjuvant approach can augment humoral immunity by modulating immunodominance and shows promise for clinical translation.

Suggested Citation

  • 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.
  • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-42923-x
    DOI: 10.1038/s41467-023-42923-x
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    References listed on IDEAS

    as
    1. Kevin O. Saunders & Esther Lee & Robert Parks & David R. Martinez & Dapeng Li & Haiyan Chen & Robert J. Edwards & Sophie Gobeil & Maggie Barr & Katayoun Mansouri & S. Munir Alam & Laura L. Sutherland , 2021. "Neutralizing antibody vaccine for pandemic and pre-emergent coronaviruses," Nature, Nature, vol. 594(7864), pages 553-559, June.
    2. 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.
    3. Joseph R. Francica & Zizhang Sheng & Zhenhai Zhang & Yoshiaki Nishimura & Masashi Shingai & Akshaya Ramesh & Brandon F. Keele & Stephen D. Schmidt & Barbara J. Flynn & Sam Darko & Rebecca M. Lynch & T, 2015. "Analysis of immunoglobulin transcripts and hypermutation following SHIVAD8 infection and protein-plus-adjuvant immunization," Nature Communications, Nature, vol. 6(1), pages 1-14, May.
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