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腺病毒载体呼吸道合胞病毒预融合糖蛋白+可溶性糖蛋白联合免疫通过IgG3建立持续的调理吞噬抗体反应。

Adenovectored RSV prefusion glycoprotein + soluble glycoprotein combination immunization establishes persistent opsonophagocytic antibody response through IgG3.

作者信息

Tong Xin, Blanc Ross, Cizmeci Deniz, Malca Hadar, Kang Jaewon, Comeaux Christy, Callendret Benoit, Bastian Arangassery Rosemary, Khan Mehak Zahoor, Alter Galit, Lingwood Daniel, McNamara Ryan P

机构信息

Ragon Institute of Mass General Brigham, MIT, and Harvard, Cambridge, MA, United States.

Department of Immunology and Infectious Diseases, Harvard T. H. Chan School of Public Health, Boston, MA, United States.

出版信息

Front Immunol. 2025 Jul 22;16:1609779. doi: 10.3389/fimmu.2025.1609779. eCollection 2025.

DOI:10.3389/fimmu.2025.1609779
PMID:40766306
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12322566/
Abstract

INTRODUCTION

Respiratory syncytial virus (RSV) causes significant lower-respiratory-tract disease in high-risk groups. A phase IIb trial showed that a combination vaccine of Ad26-vectored prefusion RSV F (Ad26.preF) plus soluble prefusion F protein (SpreF) was 80 % protective, yet the longevity and functionality of these humoral responses are unknown.

METHODS

Sera from vaccinated adults were analyzed 12 months after the primary dose and 28 days after a homologous booster at 1 year. IgG subclasses, isotypes, Fc-γ receptor (FcγR) binding, and Fc-dependent effector functions including opsinophagocytosis against RSV-F subtypes A and B were quantified via Systems Serology.

RESULTS

A single dose generated durable immunity: IgG3-driven opsonophagocytic activity and broad FcγR engagement (via IgG1, IgG2, and IgG3) persisted through 12 months without appreciable decay. The booster did not increase antibody titres, FcγR binding, or functional activity, indicating that the primary response had already plateaued.

DISCUSSION

One dose of Ad26.preF + SpreF elicits a long-lasting, functionally potent humoral response that is not further enhanced by a booster at 12 months, suggesting limited benefit from early re-vaccination. Continued follow-up will clarify the duration of protection and inform booster timing in vulnerable populations.

摘要

引言

呼吸道合胞病毒(RSV)在高危人群中可引发严重的下呼吸道疾病。一项IIb期试验表明,腺病毒26载体预融合RSV F(Ad26.preF)加可溶性预融合F蛋白(SpreF)的联合疫苗具有80%的保护效力,但这些体液免疫反应的持久性和功能尚不清楚。

方法

对接种疫苗的成年人在首剂接种后12个月以及1年后进行同源加强免疫接种28天后的血清进行分析。通过系统血清学方法对IgG亚类、同种型、Fc-γ受体(FcγR)结合以及包括针对RSV-F A和B亚型的调理吞噬作用在内的Fc依赖性效应功能进行定量分析。

结果

单剂量疫苗可产生持久免疫力:由IgG3驱动的调理吞噬活性以及广泛的FcγR结合(通过IgG1、IgG2和IgG3)在12个月内持续存在且无明显衰减。加强免疫并未提高抗体滴度、FcγR结合或功能活性,这表明初次免疫反应已达到平台期。

讨论

一剂Ad26.preF + SpreF可引发持久、功能强大的体液免疫反应,12个月时的加强免疫并未进一步增强该反应,这表明早期再次接种的益处有限。持续的随访将明确保护持续时间,并为易感人群的加强免疫时机提供依据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f026/12322566/03a0acb95568/fimmu-16-1609779-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f026/12322566/fc707c651adf/fimmu-16-1609779-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f026/12322566/dcde286684f1/fimmu-16-1609779-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f026/12322566/f9685147ca78/fimmu-16-1609779-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f026/12322566/03a0acb95568/fimmu-16-1609779-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f026/12322566/fc707c651adf/fimmu-16-1609779-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f026/12322566/dcde286684f1/fimmu-16-1609779-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f026/12322566/f9685147ca78/fimmu-16-1609779-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f026/12322566/03a0acb95568/fimmu-16-1609779-g004.jpg

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