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评估针对宋内志贺菌实验性疫苗的免疫标志物，以确定预防志贺菌病的潜在相关因素。

Putative correlates of protection against shigellosis assessing immunomarkers across responses to S. sonnei investigational vaccine.

作者信息

Conti Valentino, Rossi Omar, Clarkson Kristen A, Mancini Francesca, Nakakana Usman N, Sarakinou Eleanna, Callegaro Andrea, Ferruzzi Pietro, Acquaviva Alessandra, Arora Ashwani Kumar, Marchetti Elisa, Necchi Francesca, Frenck Robert W, Martin Laura B, Kaminski Robert W, Podda Audino, Micoli Francesca

机构信息

GSK Vaccines Institute for Global Health, Siena, Italy.

Department of Diarrheal Disease Research, Bacterial Diseases Branch, Walter Reed Army Institute of Research, Silver Spring, MD, USA.

出版信息

NPJ Vaccines. 2024 Mar 8;9(1):56. doi: 10.1038/s41541-024-00822-2.

DOI:10.1038/s41541-024-00822-2
PMID:38459072
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10923941/
Abstract

Shigella spp. are a leading bacterial cause of diarrhea. No widely licensed vaccines are available and there is no generally accepted correlate of protection. We tested a S. sonnei Generalized Modules for Membrane Antigen (GMMA)-based vaccine (1790GAHB) in a phase 2b, placebo-controlled, randomized, controlled human infection model study (NCT03527173) enrolling healthy United States adults aged 18-50 years. We report analyses evaluating immune responses to vaccination, with the aim to identify correlates of risk for shigellosis among assessed immunomarkers. We found that 1790GAHB elicited S. sonnei lipopolysaccharide specific α4β7+ immunoglobulin (Ig) G and IgA secreting B cells which are likely homing to the gut, indicating the ability to induce a mucosal in addition to a systemic response, despite parenteral delivery. We were unable to establish or confirm threshold levels that predict vaccine efficacy facilitating the evaluation of vaccine candidates. However, serum anti-lipopolysaccharide IgG and bactericidal activity were identified as potential correlates of risk for shigellosis.

摘要

志贺氏菌属是腹泻的主要细菌病因。目前尚无广泛许可使用的疫苗，也没有普遍认可的保护相关性指标。我们在美国一项2b期、安慰剂对照、随机、受控人体感染模型研究（NCT03527173）中，对一种基于宋内志贺氏菌膜抗原通用模块（GMMA）的疫苗（1790GAHB）进行了测试，该研究招募了年龄在18至50岁的美国健康成年人。我们报告了评估疫苗免疫反应的分析结果，目的是在评估的免疫标志物中确定志贺氏菌病的风险相关性指标。我们发现，1790GAHB可诱导产生宋内志贺氏菌脂多糖特异性α4β7 +免疫球蛋白（Ig）G和分泌IgA的B细胞，这些细胞可能归巢至肠道，这表明尽管通过肠胃外给药，但该疫苗除了能引发全身反应外，还能够诱导黏膜反应。我们无法确定或确认预测疫苗效力的阈值水平，这不利于对候选疫苗进行评估。然而，血清抗脂多糖IgG和杀菌活性被确定为志贺氏菌病风险的潜在相关性指标。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2830/10923941/6743b4faa6dc/41541_2024_822_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2830/10923941/12e0af89ac4c/41541_2024_822_Fig1_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2830/10923941/ea0d237e7e4f/41541_2024_822_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2830/10923941/30147bd1b617/41541_2024_822_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2830/10923941/c854370be3dd/41541_2024_822_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2830/10923941/6743b4faa6dc/41541_2024_822_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2830/10923941/12e0af89ac4c/41541_2024_822_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2830/10923941/ee02337eabb8/41541_2024_822_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2830/10923941/ea0d237e7e4f/41541_2024_822_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2830/10923941/30147bd1b617/41541_2024_822_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2830/10923941/c854370be3dd/41541_2024_822_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2830/10923941/6743b4faa6dc/41541_2024_822_Fig6_HTML.jpg

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