AUTHOR=Ji Zhenhua , Jian Miaomiao , Chen Taigui , Luo Lisha , Li Lianbao , Dai Xiting , Bai Ruolan , Ding Zhe , Bi Yunfeng , Wen Shiyuan , Zhou Guozhong , Abi Manzama-Esso , Liu Aihua , Bao Fukai 

TITLE=Immunogenicity and Safety of the M72/AS01E Candidate Vaccine Against Tuberculosis: A Meta-Analysis

JOURNAL=Frontiers in Immunology

VOLUME=Volume 10 - 2019

YEAR=2019

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2019.02089

DOI=10.3389/fimmu.2019.02089

ISSN=1664-3224

ABSTRACT=Background: Currently, there is no tuberculosis (TB) vaccine recommended for use in latent TB infections and healthy adults. M72/AS01E is a new peptide vaccine currently under development, which may improve protection against TB disease. This vaccine has been investigated in several phase I/II clinical trials. We conducted a meta-analysis to clarify the immunogenicity and safety of the M72/AS01E peptide vaccine. 
Methods: We searched the PubMed, Embase, and Cochrane Library databases for published studies (until December 2018) investigating this candidate vaccine. A meta-analysis was performed using the standard methods and procedures established by the Cochrane Collaboration.
Results: Seven eligible studies – involving 4,590 participants – were selected. The analysis revealed a vaccine immunogenicity of 58.90%, significantly higher abundance of M72-specific CD4+ T cells (standardized mean difference [SMD]=2.58) in the vaccine group versus the control group, the highest seropositivity rate (74.87%) at 1 month after the second dose of vaccination (Day 60), and sustained elevated anti-M72 IgG geometric mean concentration at study end (Day 210) (SWD=4.94). Compared with the control, participants who received vaccination were at increased risk of local injection site redness (relative risk [RR]=5.99), local swelling (RR=7.57), malaise (RR=3.01), and fatigue (RR=3.17). However, they were not at increased risk of headache (RR=1.57), myalgia (RR=0.97), and pain (RR=3.02). 
Conclusion: The M72/AS01E vaccine against TB is safe and effective. Although the vaccine is associated with a mild adverse reaction, it is promising for the prevention of TB in healthy adults. 
Keywords: vaccine, tuberculosis, M72/AS01E, immunogenicity, safety