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猴痘病毒感染后长达1年的体液免疫和细胞免疫反应动力学。

Kinetics of the humoral and cellular immune response up to 1 year from mpox virus infection.

作者信息

Mazzotta Valentina, Matusali Giulia, Cimini Eleonora, Colavita Francesca, Esvan Rozenn, Notari Stefania, Micheli Giulia, Bettini Aurora, Tartaglia Eleonora, Giacinta Alessandro, Casetti Rita, Vita Serena, Grassi Germana, Mariotti Davide, Oliva Alessandra, Paulicelli Jessica, Prota Gianluca, Girardi Enrico, Nicastri Emanuele, Maggi Fabrizio, Antinori Andrea

机构信息

Clinical Infectious Diseases Department, National Institute for Infectious Diseases "Lazzaro Spallanzani"-IRCCS, Rome, Italy.

Laboratory of Virology, National Institute for Infectious Diseases "Lazzaro Spallanzani"-IRCCS, Rome, Italy.

出版信息

Clin Microbiol Infect. 2025 Aug;31(8):1356-1362. doi: 10.1016/j.cmi.2025.04.026. Epub 2025 Apr 26.

Abstract

OBJECTIVES

The immunological signature of mpox Clade IIb was described in the early stages of infection. We aimed to characterize the kinetics of both humoral and cellular immune responses against mpox from the onset of symptoms up to one year later.

METHODS

Sixty-nine patients with mpox infected with Clade IIb during the 2022 outbreak were included in a longitudinal study. Blood samples were collected during the first 3 weeks and 3-4 (T3-4M), 6-8 (T6-8M), and 12 months (T12M) after infection. Mpox-specific IgM, IgA, IgG, and neutralizing antibodies (nAbs) titres were measured by immunofluorescence assay and 50% plaque reduction neutralization test. Interferon-γ producing specific T-cells to Modified Vaccinia Ankara (MVA) peptides was assessed by ELISpot assay. CD4+ and CD8+ T-cells phenotypic markers (CD38/CD57/PD-1) were performed by flow cytometry.

RESULTS

All the humoral markers were detected as early as 4 days and peaked at week 2 (IgG) or 3 (IgM, IgA, nAbs) from symptoms onset. At T3-4M from onset, the antibody levels decreased, and IgM was detected in only one patient; IgA in 50% (13/26), IgG and nAbs in 92% (24/26) of participants. Further decreases in IgG and nAb mean titres were observed at 6-8M. At T12M, IgM, IgA, IgG, and nAbs were detected in 4 (2/47), 48 (23/47), 93 (44/47) and 78% (37/47) of patients, respectively. MVA-specific T-cell response was detected early in the acute phase of infection, peaked at T3M and are maintained until T12M.

DISCUSSION

These data provide evidence of persistence of humoral and cellular immune response 1 year after natural infection, suggesting the maintenance of adequate immune memory. Further study is needed to assess longer persistence of immunity and the cross-protection against different mpox clades.

摘要

目的

在感染的早期阶段描述了猴痘IIb分支的免疫特征。我们旨在从症状出现直至一年后,对针对猴痘的体液免疫和细胞免疫反应的动力学特征进行描述。

方法

69例在2022年疫情期间感染IIb分支猴痘的患者纳入一项纵向研究。在感染后的前3周以及感染后3至4个月(T3 - 4M)、6至8个月(T6 - 8M)和12个月(T12M)采集血样。通过免疫荧光测定法和50%蚀斑减少中和试验测量猴痘特异性IgM、IgA、IgG和中和抗体(nAbs)滴度。通过酶联免疫斑点测定法评估针对改良安卡拉痘苗病毒(MVA)肽产生干扰素-γ的特异性T细胞。通过流式细胞术检测CD4 +和CD8 + T细胞表型标志物(CD38/CD57/PD - 1)。

结果

所有体液标志物最早在症状出现后4天即可检测到,并在第2周(IgG)或第3周(IgM、IgA、nAbs)达到峰值。从症状出现开始至T3 - 4M时,抗体水平下降,仅1例患者检测到IgM;50%(13/26)的参与者检测到IgA,92%(24/26)的参与者检测到IgG和nAbs。在6 - 8M时观察到IgG和nAb平均滴度进一步下降。在T12M时,分别在4%(2/47)、48%(23/47)、93%(44/47)和78%(37/47)的患者中检测到IgM、IgA、IgG和nAbs。MVA特异性T细胞反应在感染急性期早期即可检测到,在T3M时达到峰值,并持续至T12M。

讨论

这些数据提供了自然感染1年后体液免疫和细胞免疫反应持续存在的证据,表明存在足够的免疫记忆。需要进一步研究以评估免疫力的更长持续时间以及针对不同猴痘分支的交叉保护作用。

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