Development of a Chimeric Vaccine Against Pseudomonas aeruginosa Based on the Th17-Stimulating Epitopes of PcrV and AmpC.

• 影响指数: 8.786
• 发表时间: 2020
• 来源期刊: Front Immunol
• DOI: 10.3389/fimmu.2020.601601
• PMID: 33552056
• 文章类型: Journal Article
• 中科院分区: Q2
• 方向: 医学
• 作者列表: Wang Y,Cheng X,Wan C,Wei J,Gao C,Zhang Y,Zeng H,Peng L,Luo P,Lu D,Zou Q,Gu J

关键词: Pseudomonas aeruginosa; Th17 responses; chimeric vaccine; epitope analysis; pulmonary infection

Mesh: Animals; Antigens, Bacterial / genetics immunology; Bacterial Proteins / genetics immunology; Bacterial Toxins / genetics immunology; Epitopes, T-Lymphocyte / genetics immunology; Female; Mice; Mice, Knockout; Pore Forming Cytotoxic Proteins / genetics immunology; Pseudomonas Vaccines / genetics immunology; Pseudomonas aeruginosa / genetics immunology; Th17 Cells / immunology; beta-Lactamases / genetics immunology

Abstract

Pulmonary infection caused by Pseudomonas aeruginosa (PA) has created an urgent need for an efficient vaccine, but the protection induced by current candidates is limited, partially because of the high variability of the PA genome. Antigens targeting pulmonary Th17 responses are able to provide antibody-independent and broad-spectrum protection; however, little information about Th17-stimulating antigens in PA is available. Herein, we identified two novel PA antigens that effectively induce Th17-dependent protection, namely, PcrV (PA1706) and AmpC (PA4110). Compared to intramuscular immunization, intranasal immunization enhanced the protection of rePcrV due to activation of a Th17 response. The Th17-stimulating epitopes of PcrV and AmpC were identified, and the recombinant protein PVAC was designed and generated by combining these Th17-stimulating epitopes. PVAC was successfully produced in soluble form and elicited broad protective immunity against PA. Our results provide an alternative strategy for the development of Th17-based vaccines against PA and other pathogens.