Nature Communications (Nov 2023)
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,
- Shane Crotty
Affiliations
- Ivy Phung
- Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology (LJI)
- Kristen A. Rodrigues
- Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology
- Ester Marina-Zárate
- Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology (LJI)
- Laura Maiorino
- Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology
- Bapi Pahar
- Tulane National Primate Research Center, Tulane School of Medicine
- Wen-Hsin Lee
- Department of Integrative Structural and Computational Biology, The Scripps Research Institute
- Mariane Melo
- Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute
- Amitinder Kaur
- Tulane National Primate Research Center, Tulane School of Medicine
- Carolina Allers
- Tulane National Primate Research Center, Tulane School of Medicine
- Marissa Fahlberg
- Tulane National Primate Research Center, Tulane School of Medicine
- Brooke F. Grasperge
- Tulane National Primate Research Center, Tulane School of Medicine
- Jason P. Dufour
- Tulane National Primate Research Center, Tulane School of Medicine
- Faith Schiro
- Tulane National Primate Research Center, Tulane School of Medicine
- Pyone P. Aye
- Tulane National Primate Research Center, Tulane School of Medicine
- Paul G. Lopez
- Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology (LJI)
- Jonathan L. Torres
- Department of Integrative Structural and Computational Biology, The Scripps Research Institute
- Gabriel Ozorowski
- Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute
- Saman Eskandarzadeh
- Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute
- Michael Kubitz
- Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute
- Erik Georgeson
- Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute
- Bettina Groschel
- Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute
- Rebecca Nedellec
- Department of Immunology and Microbiology, The Scripps Research Institute
- Michael Bick
- Department of Immunology and Microbiology, The Scripps Research Institute
- Katarzyna Kaczmarek Michaels
- Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology
- Hongmei Gao
- Department of Surgery, Laboratory for AIDS Vaccine Research & Development, Duke University Medical Center, Duke University
- Xiaoying Shen
- Department of Surgery, Laboratory for AIDS Vaccine Research & Development, Duke University Medical Center, Duke University
- Diane G. Carnathan
- Emory National Primate Research Center and Emory Vaccine Center, Emory University School of Medicine
- Guido Silvestri
- Emory National Primate Research Center and Emory Vaccine Center, Emory University School of Medicine
- David C. Montefiori
- Department of Surgery, Laboratory for AIDS Vaccine Research & Development, Duke University Medical Center, Duke University
- Andrew B. Ward
- Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute
- Lars Hangartner
- Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute
- Ronald S. Veazey
- Tulane National Primate Research Center, Tulane School of Medicine
- Dennis R. Burton
- Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute
- William R. Schief
- Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute
- Darrell J. Irvine
- Consortium for HIV/AIDS Vaccine Development (CHAVD), The Scripps Research Institute
- Shane Crotty
- Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology (LJI)
- DOI
- https://doi.org/10.1038/s41467-023-42923-x
- Journal volume & issue
-
Vol. 14,
no. 1
pp. 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.