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

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. Dufour, Faith Schiro, Pyone P. Aye, Paul G. Lopez, Jonathan L. Torres, Gabriel Ozorowski, Saman Eskandarzadeh, Michael Kubitz, Erik Georgeson, Bettina Groschel, Rebecca Nedellec, Michael Bick, Katarzyna Kaczmarek Michaels, Hongmei Gao, Xiaoying Shen, Diane G. Carnathan, Guido Silvestri, David C. Montefiori, Andrew B. Ward, Lars Hangartner, Ronald S. Veazey, Dennis R. Burton, William R. Schief, Darrell J. Irvine () and Shane Crotty ()
Additional contact information
Ivy Phung: La Jolla Institute for Immunology (LJI)
Kristen A. Rodrigues: Massachusetts Institute of Technology
Ester Marina-Zárate: La Jolla Institute for Immunology (LJI)
Laura Maiorino: Massachusetts Institute of Technology
Bapi Pahar: Tulane School of Medicine
Wen-Hsin Lee: The Scripps Research Institute
Mariane Melo: The Scripps Research Institute
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
Saman Eskandarzadeh: The Scripps Research Institute
Michael Kubitz: The Scripps Research Institute
Erik Georgeson: The Scripps Research Institute
Bettina Groschel: The Scripps Research Institute
Rebecca Nedellec: The Scripps Research Institute
Michael Bick: The Scripps Research Institute
Katarzyna Kaczmarek Michaels: Massachusetts Institute of Technology
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
Lars Hangartner: The Scripps Research Institute
Ronald S. Veazey: Tulane School of Medicine
Dennis R. Burton: The Scripps Research Institute
William R. Schief: The Scripps Research Institute
Darrell J. Irvine: The Scripps Research Institute
Shane Crotty: La Jolla Institute for Immunology (LJI)

Nature Communications, 2023, vol. 14, issue 1, 1-15

Abstract: 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.

Date: 2023
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DOI: 10.1038/s41467-023-42923-x

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