Production and efficacy of a low-cost recombinant pneumococcal protein polysaccharide conjugate vaccine

被引:33
作者
Herbert, Jenny A. [1 ,6 ]
Kay, Emily J. [2 ]
Faustini, Sian E. [3 ,4 ]
Richter, Alex [3 ,4 ,5 ]
Abouelhadid, Sherif [2 ]
Cuccui, Jon [2 ]
Wren, Brendan [2 ]
Mitchell, Timothy J. [1 ]
机构
[1] Univ Birmingham, Inst Microbiol & Infect, Coll Med & Dent Sci, Birmingham, W Midlands, England
[2] London Sch Hyg & Trop Med, Dept Pathogen Mol Biol, London, England
[3] Univ Birmingham, Inst Immunol & Immunotherapy, Coll Med & Dent Sci, Birmingham, W Midlands, England
[4] Queen Elizabeth Hosp, Dept Immunol, Birmingham, W Midlands, England
[5] Univ Hosp Birmingham NHS Fdn Trust, Birmingham, W Midlands, England
[6] UCL Great Ormond St Inst Child Hlth, London, England
基金
英国医学研究理事会;
关键词
Streptococcus pneumoniae; Conjugate vaccine; Protein glycan coupling technology; Glycoengineering; Pneumonia; INFLUENZAE TYPE-B; STREPTOCOCCUS-PNEUMONIAE; HAEMOPHILUS-INFLUENZAE; CHILDREN YOUNGER; OPSONIC ACTIVITY; UNITED-STATES; IMMUNOGENICITY; DISEASE; GLYCOSYLATION; ANTIBODIES;
D O I
10.1016/j.vaccine.2018.05.036
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Streptococcus pneumoniae is the leading cause of bacterial pneumonia. Although this is a vaccine preventable disease, S. pneumoniae still causes over 1 million deaths per year, mainly in children under the age of five. The biggest disease burden is in the developing world, which is mainly due to unavailability of vaccines due to their high costs. Protein polysaccharide conjugate vaccines are given routinely in the developed world to children to induce a protective antibody response against S. pneumoniae. One of these vaccines is Prevnar13, which targets 13 of the 95 known capsular types. Current vaccine production requires growth of large amounts of the 13 serotypes, and isolation of the capsular polysaccharide that is then chemically coupled to a protein, such as the diphtheria toxoid CRM197, in a multistep expensive procedure. In this study, we design, purify and produce novel recombinant pneumococcal protein polysaccharide conjugate vaccines in Escherichia coli, which act as mini factories for the low-cost production of conjugate vaccines. Recombinant vaccine efficacy was tested in a murine model of pneumococcal pneumonia; ability to protect against invasive disease was compared to that of Prevnar13. This study provides the first proof of principle that protein polysaccharide conjugate vaccines produced in E. coli can be used to prevent pneumococcal infection. Vaccines produced in this manner may provide a low-cost alternative to the current vaccine production methodology. (C) 2018 The Authors. Published by Elsevier Ltd.
引用
收藏
页码:3809 / 3819
页数:11
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