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自组装肽纳米纤维 HIV 疫苗可引发强大的疫苗诱导抗体功能，并调节 Fc 糖基化。

Self-assembling peptide nanofiber HIV vaccine elicits robust vaccine-induced antibody functions and modulates Fc glycosylation.

机构信息

Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA.

Department of Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, NC 27710, USA.

出版信息

Sci Adv. 2022 Sep 23;8(38):eabq0273. doi: 10.1126/sciadv.abq0273.

DOI:10.1126/sciadv.abq0273
PMID:36149967
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9506727/
Abstract

To develop vaccines for certain key global pathogens such as HIV, it is crucial to elicit both neutralizing and non-neutralizing Fc-mediated effector antibody functions. Clinical evidence indicates that non-neutralizing antibody functions including antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP) contribute to protection against several pathogens. In this study, we demonstrated that conjugation of HIV Envelope (Env) antigen gp120 to a self-assembling nanofiber material named Q11 induced antibodies with higher breadth and functionality when compared to soluble gp120. Immunization with Q11-conjugated gp120 vaccine (gp120-Q11) demonstrated higher tier 1 neutralization, ADCP, and ADCC as compared to soluble gp120. Moreover, Q11 conjugation altered the Fc N-glycosylation profile of antigen-specific antibodies, leading to a phenotype associated with increased ADCC in animals immunized with gp120-Q11. Thus, this nanomaterial vaccine strategy can enhance non-neutralizing antibody functions possibly through modulation of immunoglobulin G Fc N-glycosylation.

摘要

为了开发针对 HIV 等某些关键全球病原体的疫苗，诱导体液中和及非中和 Fc 介导的效应抗体功能至关重要。临床证据表明，非中和抗体功能，包括抗体依赖的细胞毒性（ADCC）和抗体依赖的细胞吞噬作用（ADCP），有助于预防几种病原体。在这项研究中，我们证明了将 HIV 包膜（Env）抗原 gp120 与一种名为 Q11 的自组装纳米纤维材料偶联，可诱导产生比可溶性 gp120 具有更广泛和更有效的抗体。与可溶性 gp120 相比，用 Q11 偶联的 gp120 疫苗（gp120-Q11）免疫可诱导更高的 1 型中和、ADCP 和 ADCC。此外，Q11 偶联改变了抗原特异性抗体的 Fc N-糖基化谱，导致与用 gp120-Q11 免疫的动物中增强的 ADCC 相关的表型。因此，这种纳米材料疫苗策略可以通过调节免疫球蛋白 G Fc N-糖基化来增强非中和抗体功能。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c710/9506727/ed4b36569473/sciadv.abq0273-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c710/9506727/f773ee30e81b/sciadv.abq0273-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c710/9506727/8621fa5c3506/sciadv.abq0273-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c710/9506727/692d8f5d0303/sciadv.abq0273-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c710/9506727/687723f800c3/sciadv.abq0273-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c710/9506727/e008de5e2595/sciadv.abq0273-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c710/9506727/ed4b36569473/sciadv.abq0273-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c710/9506727/f773ee30e81b/sciadv.abq0273-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c710/9506727/8621fa5c3506/sciadv.abq0273-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c710/9506727/692d8f5d0303/sciadv.abq0273-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c710/9506727/687723f800c3/sciadv.abq0273-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c710/9506727/e008de5e2595/sciadv.abq0273-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c710/9506727/ed4b36569473/sciadv.abq0273-f6.jpg

相似文献

[1]
Self-assembling peptide nanofiber HIV vaccine elicits robust vaccine-induced antibody functions and modulates Fc glycosylation.

Sci Adv. 2022-9-23

[2]
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Clin Vaccine Immunol. 2017-6-5

[3]
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J Virol. 2018-2-12

[4]
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Front Immunol. 2020

[5]
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[6]
VH1-69 Utilizing Antibodies Are Capable of Mediating Non-neutralizing Fc-Mediated Effector Functions Against the Transmitted/Founder gp120.

Front Immunol. 2019-1-15

[7]
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[8]
Fc Receptor-Mediated Activities of Env-Specific Human Monoclonal Antibodies Generated from Volunteers Receiving the DNA Prime-Protein Boost HIV Vaccine DP6-001.

J Virol. 2016-10-28

[9]
Bridging Vaccine-Induced HIV-1 Neutralizing and Effector Antibody Responses in Rabbit and Rhesus Macaque Animal Models.

J Virol. 2019-5-1

[10]
HIV Broadly Neutralizing Antibodies Expressed as IgG3 Preserve Neutralization Potency and Show Improved Fc Effector Function.

Front Immunol. 2021

引用本文的文献

[1]
Self-Assembling Aromatic Peptide Amphiphile Fibers for Multivalent Display of Enzymatically Linked Antigenic Proteins.

ACS Appl Mater Interfaces. 2025-8-6

[2]
Advanced Nanomedicines for Treating Refractory Inflammation-Related Diseases.

Nanomicro Lett. 2025-7-7

[3]
Nanotechnology-based strategies for vaccine development: accelerating innovation and delivery.

Biomater Transl. 2025-3-25

[4]
Evaluation of cylindrical micelles assembled from amphiphilic β-peptides as antigen delivery nanostructures.

Nanoscale Adv. 2025-3-20

[5]
A TLR7 Agonist Conjugated to a Nanofibrous Peptide Hydrogel as a Potent Vaccine Adjuvant.

Adv Healthc Mater. 2025-1

[6]
Clinical glycoproteomics: methods and diseases.

MedComm (2020). 2024-10-4

[7]
Therapeutic Supramolecular Polymers: Designs and Applications.

Prog Polym Sci. 2024-1

[8]
Polyfunctional antibodies: a path towards precision vaccines for vulnerable populations.

Front Immunol. 2023

[9]
Chemical and biological conjugation strategies for the development of multivalent protein vaccine nanoparticles.

Biopolymers. 2023-8

本文引用的文献

[1]
A particulate saponin/TLR agonist vaccine adjuvant alters lymph flow and modulates adaptive immunity.

Sci Immunol. 2021-12-3

[2]
HIV envelope antigen valency on peptide nanofibers modulates antibody magnitude and binding breadth.

Sci Rep. 2021-7-14

[3]
Antibody fucosylation predicts disease severity in secondary dengue infection.

Science. 2021-6-4

[4]
High titers and low fucosylation of early human anti-SARS-CoV-2 IgG promote inflammation by alveolar macrophages.

Sci Transl Med. 2021-6-2

[5]
Modular complement assemblies for mitigating inflammatory conditions.

Proc Natl Acad Sci U S A. 2021-4-13

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Vaccine Efficacy of ALVAC-HIV and Bivalent Subtype C gp120-MF59 in Adults.

N Engl J Med. 2021-3-25

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Two Randomized Trials of Neutralizing Antibodies to Prevent HIV-1 Acquisition.

N Engl J Med. 2021-3-18

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Afucosylated IgG characterizes enveloped viral responses and correlates with COVID-19 severity.

Science. 2021-2-26

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Proinflammatory IgG Fc structures in patients with severe COVID-19.

Nat Immunol. 2021-1

[10]
Antibody binding to native cytomegalovirus glycoprotein B predicts efficacy of the gB/MF59 vaccine in humans.

Sci Transl Med. 2020-11-4

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