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结核亚单位疫苗 M72/AS01 和 MVA85A 的免疫原性和安全性的系统评价和荟萃分析。

The Systematic Review and Meta-Analysis on the Immunogenicity and Safety of the Tuberculosis Subunit Vaccines M72/AS01 and MVA85A.

机构信息

Lanzhou Center for Tuberculosis Research and Institute of Pathogen Biology, School of Basic Medical Sciences, Lanzhou University, Lanzhou, China.

Gansu Provincial Key Laboratory of Evidence Based Medicine and Clinical Translation, Lanzhou University, Lanzhou, China.

出版信息

Front Immunol. 2020 Oct 8;11:1806. doi: 10.3389/fimmu.2020.01806. eCollection 2020.


DOI:10.3389/fimmu.2020.01806
PMID:33133057
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7578575/
Abstract

Tuberculosis (TB) is a severe infectious disease with devastating effects on global public health. No TB vaccine has yet been approved for use on latent TB infections and healthy adults. In this study, we performed a systematic review and meta-analysis to evaluate the immunogenicity and safety of the M72/AS01 and MVA85A subunit vaccines. The M72/AS01 is a novel peptide-based vaccine currently in progress, which may increase the protection level against TB infection. The MVA85A was a viral vector-based TB subunit vaccine being used in the clinical trials. The vaccines mentioned above have been studied in various phase I/II clinical trials. Immunogenicity and safety is the first consideration for TB vaccine development. The PubMed, Embase, and Cochrane Library databases were searched for published studies (until October 2019) to find out information on the M72/AS01 and MVA85A candidate vaccines. The meta-analysis was conducted by applying the standard methods and processes established by the Cochrane Collaboration. Five eligible randomized clinical trials (RCTs) were selected for the meta-analysis of M72/AS01E candidate vaccines. The analysis revealed that the M72/AS01E subunit vaccine had an abundance of polyfunctional M72-specific CD4+ T cells [standardized mean difference (SMD) = 2.37] in the vaccine group versus the control group, the highest seropositivity rate [relative risk (RR) = 5.09]. The M72/AS01E vaccinated group were found to be at high risk of local injection site redness (RR = 2.64), headache (RR = 1.59), malaise (RR = 3.55), myalgia (RR = 2.27), fatigue (RR = 2.16), pain (RR = 3.99), swelling (RR = 5.09), and fever (RR = 2.04) compared to the control groups. The incidences of common adverse events of M72/AS01E were local injection site redness, headache, malaise, myalgia, fatigue, pain, swelling, fever, etc. Six eligible RCTs were selected for the meta-analysis on MVA85A candidate vaccines. The analysis revealed that the subunit vaccine MVA85A had a higher abundance of overall pooled proportion polyfunctional MVA85A-specific CD4+ T cells SMD = 2.41 in the vaccine group vs. the control group, with the highest seropositivity rate [estimation rate (ER) = 0.55]. The MVA85A vaccinated group were found to be at high risk of local injection site redness (ER = 0.55), headache (ER = 0.40), malaise (ER = 0.29), pain (ER = 0.54), myalgia (ER = 0.31), and fever (ER = 0.20). The incidences of common adverse events of MVA85A were local injection site redness, headache, malaise, pain, myalgia, fever, etc. The M72/AS01 and MVA85A vaccines against TB are safe and had immunogenicity in diverse clinical trials. The M72/AS01 and MVA85A vaccines are associated with a mild adverse reaction. The meta-analysis on immunogenicity and safety of M72/AS01 and MVA85A vaccines provides useful information for the evaluation of available subunit vaccines in the clinic.

摘要

结核病(TB)是一种严重的传染病,对全球公共卫生造成了破坏性影响。目前尚无针对潜伏性结核感染和健康成年人的 TB 疫苗获得批准。在这项研究中,我们进行了系统评价和荟萃分析,以评估 M72/AS01 和 MVA85A 亚单位疫苗的免疫原性和安全性。M72/AS01 是一种新型的基于肽的疫苗,目前正在进行研究,可能会提高对 TB 感染的保护水平。MVA85A 是一种基于病毒载体的 TB 亚单位疫苗,正在临床试验中使用。上述疫苗已在各种 I/II 期临床试验中进行了研究。免疫原性和安全性是 TB 疫苗开发的首要考虑因素。我们检索了 PubMed、Embase 和 Cochrane Library 数据库中发表的研究(截至 2019 年 10 月),以获取有关 M72/AS01 和 MVA85A 候选疫苗的信息。荟萃分析采用了 Cochrane 协作组织制定的标准方法和流程进行。我们选择了五项合格的随机临床试验(RCT)进行 M72/AS01E 候选疫苗的荟萃分析。分析显示,M72/AS01E 亚单位疫苗在疫苗组中具有丰富的多效性 M72 特异性 CD4+T 细胞[标准化均数差(SMD)=2.37],血清阳性率最高[相对风险(RR)=5.09]。与对照组相比,M72/AS01E 疫苗接种组存在局部注射部位发红(RR=2.64)、头痛(RR=1.59)、不适(RR=3.55)、肌痛(RR=2.27)、疲劳(RR=2.16)、疼痛(RR=3.99)、肿胀(RR=5.09)和发热(RR=2.04)的高风险。M72/AS01E 的常见不良反应包括局部注射部位发红、头痛、不适、肌痛、疲劳、疼痛、肿胀、发热等。我们选择了六项合格的 RCT 进行 MVA85A 候选疫苗的荟萃分析。分析显示,亚单位疫苗 MVA85A 在疫苗组中具有更高的总体聚集比例多效性 MVA85A 特异性 CD4+T 细胞 SMD=2.41,血清阳性率最高[估计率(ER)=0.55]。与对照组相比,MVA85A 疫苗接种组存在局部注射部位发红(ER=0.55)、头痛(ER=0.40)、不适(ER=0.29)、疼痛(ER=0.54)、肌痛(ER=0.31)和发热(ER=0.20)的高风险。MVA85A 的常见不良反应包括局部注射部位发红、头痛、不适、疼痛、肌痛、发热等。M72/AS01 和 MVA85A 疫苗对结核病具有安全性和免疫原性,在不同的临床试验中均有表现。M72/AS01 和 MVA85A 疫苗与轻度不良反应相关。对 M72/AS01 和 MVA85A 疫苗的免疫原性和安全性的荟萃分析为评估临床中可用的亚单位疫苗提供了有用的信息。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe9d/7578575/392572a033c0/fimmu-11-01806-g0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe9d/7578575/25e5cf002b18/fimmu-11-01806-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe9d/7578575/5c1cb1796f5a/fimmu-11-01806-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe9d/7578575/2451ffeae00a/fimmu-11-01806-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe9d/7578575/cb37c9d93d16/fimmu-11-01806-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe9d/7578575/17b1554e00ec/fimmu-11-01806-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe9d/7578575/392572a033c0/fimmu-11-01806-g0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe9d/7578575/25e5cf002b18/fimmu-11-01806-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe9d/7578575/5c1cb1796f5a/fimmu-11-01806-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe9d/7578575/2451ffeae00a/fimmu-11-01806-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe9d/7578575/cb37c9d93d16/fimmu-11-01806-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe9d/7578575/17b1554e00ec/fimmu-11-01806-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fe9d/7578575/392572a033c0/fimmu-11-01806-g0006.jpg

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Long-term safety and immunogenicity of the M72/AS01E candidate tuberculosis vaccine in HIV-positive and -negative Indian adults: Results from a phase II randomized controlled trial.

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Phase 2b Controlled Trial of M72/AS01 Vaccine to Prevent Tuberculosis.

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