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疫苗诱导的黏膜和系统记忆 NK/ILCs 可降低 SIV/SHIV 感染的风险。

Vaccine induced mucosal and systemic memory NK/ILCs elicit decreased risk of SIV/SHIV acquisition.

机构信息

Animal Models and Retroviral Vaccines Section, Vaccine Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, United States.

出版信息

Front Immunol. 2024 Sep 5;15:1441793. doi: 10.3389/fimmu.2024.1441793. eCollection 2024.

DOI:10.3389/fimmu.2024.1441793
PMID:39301032
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11410642/
Abstract

SIV and HIV-based envelope V1-deleted (ΔV1) vaccines, delivered systemically by the DNA/ALVAC/gp120 platform, decrease the risk of mucosal SIV or SHIV acquisition more effectively than V1-replete vaccines. Here we investigated the induction of mucosal and systemic memory-like NK cells as well as antigen-reactive ILC response by DNA/ALVAC/gp120-based vaccination and their role against SIV/SHIV infection. ΔV1 HIV vaccination elicited a higher level of mucosal TNF-α and CD107 memory-like NK cells than V1-replete vaccination, suggesting immunogen dependence. Mucosal memory-like NK cells, systemic granzyme B memory NK cells, and vaccine-induced mucosal envelope antigen-reactive IL-17 NKp44 ILCs, IL-17 ILC3s, and IL-13 ILC2 subsets were linked to a lower risk of virus acquisition. Additionally, mucosal memory-like NK cells and mucosal env-reactive IFN-γ ILC1s and env- reactive IL-13 ILC2 subsets correlated with viral load control. We further observed a positive correlation between post-vaccination systemic and mucosal memory-like NK cells, suggesting vaccination enhances the presence of these cells in both compartments. Mucosal and systemic memory-like NK cells positively correlated with V2-specific ADCC responses, a reproducible correlate of reduced risk of SIV/HIV infection. In contrast, an increased risk was associated with the level of mucosal PMA/Ionomycin-induced IFN-γ and CD107 NKG2ANKp44 ILCs. Plasma proteomic analyses demonstrated that suppression of mucosal memory-like NK cells was linked to the level of CCL-19, LT-α, TNFSF-12, and IL-15, suppression of systemic env-reactive granzyme B memory-like NK cells was associated with the level of OLR1, CCL-3, and OSM, and suppression of IL-17 ILCs immunity was correlated with the level of IL-6 and CXCL-9. In contrast, FLT3 ligand was associated with promotion of protective mucosal env-reactive IL-17 responses. These findings emphasize the importance of mucosal memory-like NK cell and envelope- reactive ILC responses for protection against mucosal SIV/SHIV acquisition.

摘要

SIV 和 HIV 基于包膜 V1 缺失（ΔV1）的疫苗，通过 DNA/ALVAC/gp120 平台系统递呈，比 V1 完整疫苗更有效地降低了黏膜 SIV 或 SHIV 感染的风险。在这里，我们研究了基于 DNA/ALVAC/gp120 疫苗接种诱导黏膜和系统记忆样 NK 细胞以及抗原反应性 ILC 反应的情况，以及它们对 SIV/SHIV 感染的作用。ΔV1 HIV 疫苗接种比 V1 完整疫苗接种诱导更高水平的黏膜 TNF-α 和 CD107 记忆样 NK 细胞，表明免疫原依赖性。黏膜记忆样 NK 细胞、系统颗粒酶 B 记忆 NK 细胞以及疫苗诱导的黏膜包膜抗原反应性 IL-17 NKp44 ILC、IL-17 ILC3 和 IL-13 ILC2 亚群与较低的病毒获得风险相关。此外，黏膜记忆样 NK 细胞和黏膜 env 反应性 IFN-γ ILC1 和 env 反应性 IL-13 ILC2 亚群与病毒载量控制相关。我们进一步观察到接种后系统和黏膜记忆样 NK 细胞之间存在正相关，表明疫苗增强了这些细胞在两个隔室中的存在。黏膜和系统记忆样 NK 细胞与 V2 特异性 ADCC 反应呈正相关，这是降低 SIV/HIV 感染风险的一种可重复的相关性。相比之下，风险增加与黏膜 PMA/离子霉素诱导的 IFN-γ 和 CD107 NKG2A+NKp44 ILC 水平相关。血浆蛋白质组学分析表明，黏膜记忆样 NK 细胞的抑制与 CCL-19、LT-α、TNFSF-12 和 IL-15 的水平相关，系统 env 反应性颗粒酶 B 记忆样 NK 细胞的抑制与 OLR1、CCL-3 和 OSM 的水平相关，而 IL-17 ILC 免疫的抑制与 IL-6 和 CXCL-9 的水平相关。相反，FLT3 配体与促进保护性黏膜 env 反应性 IL-17 反应相关。这些发现强调了黏膜记忆样 NK 细胞和包膜反应性 ILC 反应对预防黏膜 SIV/SHIV 感染的重要性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d68/11410642/a6afd8572ecc/fimmu-15-1441793-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d68/11410642/0b8fdadb5860/fimmu-15-1441793-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d68/11410642/5573032aae19/fimmu-15-1441793-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d68/11410642/10be57f0bd5d/fimmu-15-1441793-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d68/11410642/4810c8103a3c/fimmu-15-1441793-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d68/11410642/0bc0ce9f81a1/fimmu-15-1441793-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d68/11410642/a6afd8572ecc/fimmu-15-1441793-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d68/11410642/0b8fdadb5860/fimmu-15-1441793-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d68/11410642/5573032aae19/fimmu-15-1441793-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d68/11410642/10be57f0bd5d/fimmu-15-1441793-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d68/11410642/4810c8103a3c/fimmu-15-1441793-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d68/11410642/0bc0ce9f81a1/fimmu-15-1441793-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7d68/11410642/a6afd8572ecc/fimmu-15-1441793-g006.jpg

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本文引用的文献

[1]
Antigen-specific memory NK cell responses against HIV and influenza use the NKG2/HLA-E axis.

Sci Immunol. 2023-12-8

[2]
In Vivo Treatment with Insulin-like Growth Factor 1 Reduces CCR5 Expression on Vaccine-Induced Activated CD4 T-Cells.

Vaccines (Basel). 2023-10-30

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HIV-Related Atherosclerosis: State-of-the-Art-Review.

Curr Probl Cardiol. 2023-9

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Cholera toxin B scaffolded, focused SIV V2 epitope elicits antibodies that influence the risk of SIV acquisition in macaques.

Front Immunol. 2023

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Front Immunol. 2023

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Front Immunol. 2023

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Vaccine plus microbicide effective in preventing vaginal SIV transmission in macaques.

Nat Microbiol. 2023-5

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Effect of Passive Administration of Monoclonal Antibodies Recognizing Simian Immunodeficiency Virus (SIV) V2 in CH59-Like Coil/Helical or β-Sheet Conformations on Time of SIV Acquisition.

J Virol. 2023-4-27

[9]
HIV vaccine candidate efficacy in female macaques mediated by cAMP-dependent efferocytosis and V2-specific ADCC.

Nat Commun. 2023-2-2

[10]
Recombinant Simian Varicella Virus-Simian Immunodeficiency Virus Vaccine Induces T and B Cell Functions and Provides Partial Protection against Repeated Mucosal SIV Challenges in Rhesus Macaques.

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