A combined adjuvant approach primes robust germinal center responses and humoral immunity in non-human primates
-
Published:2023-11-04
Issue:1
Volume:14
Page:
-
ISSN:2041-1723
-
Container-title:Nature Communications
-
language:en
-
Short-container-title:Nat Commun
Author:
Phung IvyORCID, Rodrigues Kristen A.ORCID, Marina-Zárate EsterORCID, Maiorino Laura, Pahar BapiORCID, Lee Wen-HsinORCID, Melo Mariane, Kaur Amitinder, Allers Carolina, Fahlberg Marissa, Grasperge Brooke F., Dufour Jason P., Schiro Faith, Aye Pyone P.ORCID, Lopez Paul G., Torres Jonathan L.ORCID, Ozorowski GabrielORCID, Eskandarzadeh Saman, Kubitz Michael, Georgeson ErikORCID, Groschel Bettina, Nedellec Rebecca, Bick Michael, Kaczmarek Michaels Katarzyna, Gao HongmeiORCID, Shen XiaoyingORCID, Carnathan Diane G., Silvestri GuidoORCID, Montefiori David C.ORCID, Ward Andrew B.ORCID, Hangartner LarsORCID, Veazey Ronald S.ORCID, Burton Dennis R.ORCID, Schief William R.ORCID, Irvine Darrell J.ORCID, Crotty ShaneORCID
Abstract
AbstractAdjuvants 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.
Funder
U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases
Publisher
Springer Science and Business Media LLC
Subject
General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry,Multidisciplinary
Reference52 articles.
1. Plotkin, S. A. Correlates of protection induced by vaccination▿. Clin. Vaccin. Immunol. 17, 1055–1065 (2010). 2. Burton, D. R. & Hangartner, L. Broadly neutralizing antibodies to HIV and their role in vaccine design. Annu Rev. Immunol. 34, 635–659 (2016). 3. Victora, G. D. & Nussenzweig, M. C. Germinal Centers. Annu Rev. Immunol. 40, 1–30 (2022). 4. Crotty, S. T follicular helper cell biology: a decade of discovery and diseases. Immunity 50, 1132–1148 (2019). 5. Pulendran, B., Arunachalam, P. S. & O’Hagan, D. T. Emerging concepts in the science of vaccine adjuvants. Nat. Rev. Drug Discov. 20, 454–475 (2021).
Cited by
1 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献
|
|