Development and Immunogenicity of a Prototype Multivalent Group B Streptococcus Bioconjugate Vaccine.
Development and Immunogenicity of a Prototype Multivalent Group B Streptococcus Bioconjugate Vaccine.
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DOI：
10.1021/acsinfecdis.1c00415
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发表时间：
2021-11-12
影响因子：
5.3
通讯作者：
Harding CM
中科院分区：
文献类型：
--
作者：
Duke JA;Paschall AV;Robinson LS;Knoot CJ;Vinogradov E;Scott NE;Feldman MF;Avci FY;Harding CM
B族链球菌（GBS）是全球范围内新生儿感染和非妊娠成人侵袭性疾病的主要原因。开发针对GBS胶囊的保护性缀合疫苗已经进行了30多年;然而，它尚未产生许可的产品。在这项研究中，我们提出了一种新的生物结合平台，用于生产原型多价GBS结合疫苗及其随后的分析和免疫学表征。使用糖工程策略，我们产生了重组表达Ia型、Ib型和III型GBS荚膜多糖的大肠杆菌菌株。然后我们将表达Ia、Ib和III型荚膜的E.大肠杆菌菌株与工程化的铜绿假单胞菌外毒素A（EPA）载体蛋白和PglS寡糖基转移酶。GBS胶囊、工程化EPA蛋白和PglS的共表达使得靶GBS胶囊能够共价连接到EPA上的工程化丝氨酸残基，所有这些都在E.杆菌纯化GBS生物缀合物，分析表征，并评价免疫原性和功能性抗体应答。这项概念验证研究标志着开发下一代多价GBS生物缀合物疫苗的第一步，该疫苗通过生产能够引发针对GBS胶囊的功能性抗体的缀合物进行了验证。
Group B Streptococcus (GBS) is a leading cause of neonatal infections and invasive diseases in nonpregnant adults worldwide. Developing a protective conjugate vaccine targeting the capsule of GBS has been pursued for more than 30 years; however, it has yet to yield a licensed product. In this study, we present a novel bioconjugation platform for producing a prototype multivalent GBS conjugate vaccine and its subsequent analytical and immunological characterizations. Using a glycoengineering strategy, we generated strains of Escherichia coli that recombinantly express the type Ia, type Ib, and type III GBS capsular polysaccharides. We then combined the type Ia-, Ib-, and III-capsule-expressing E. coli strains with an engineered Pseudomonas aeruginosa exotoxin A (EPA) carrier protein and the PglS oligosaccharyltransferase. Coexpression of a GBS capsule, the engineered EPA protein, and PglS enabled the covalent attachment of the target GBS capsule to an engineered serine residue on EPA, all within the periplasm of E. coli. GBS bioconjugates were purified, analytically characterized, and evaluated for immunogenicity and functional antibody responses. This proof-of-concept study signifies the first step in the development of a next-generation multivalent GBS bioconjugate vaccine, which was validated by the production of conjugates that are able to elicit functional antibodies directed against the GBS capsule.
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影响因子：
5.5
作者：
Hatz, Christoph F. R.;Bally, Bettina;Fonck, Veronica Gambillara
通讯作者：
Fonck, Veronica Gambillara
影响因子：
6.4
作者：
Buurman, Ed T.;Timofeyeva, Yekaterina;Anderson, Annaliesa S.
通讯作者：
Anderson, Annaliesa S.
B组链球菌囊类型，序列类型和表面蛋白作为潜在疫苗候选物的系统评价。
影响因子：
5.5
作者：
Bianchi-Jassir F;Paul P;To KN;Carreras-Abad C;Seale AC;Jauneikaite E;Madhi SA;Russell NJ;Hall J;Madrid L;Bassat Q;Kwatra G;Le Doare K;Lawn JE
通讯作者：
Lawn JE
影响因子：
4.3
作者：
Knoot CJ;Robinson LS;Harding CM
通讯作者：
Harding CM
影响因子：
--
作者：
Burton, Robert L.;Nahm, Moon H.
通讯作者：
Nahm, Moon H.