Boerth Emily M, Gong Joyce, Roffler Becky, Hancock Zoe, Berger Lydia, Song Boni, Malley Sasha F, MacLennan Calman A, Zhang Fan, Malley Richard, Lu Ying-Jie
Division of Infectious Diseases, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Enteric & Diarrheal Diseases, Global Health, Bill & Melinda Gates Foundation, 500 5th Ave. N, Seattle, WA 98109, USA.
Vaccines (Basel). 2024 Sep 24;12(10):1091. doi: 10.3390/vaccines12101091.
Shigellosis is the leading cause of diarrheal deaths worldwide and is particularly dangerous in children under 5 years of age in low- and middle-income countries. Additionally, the rise in antibiotic resistance has highlighted the need for an effective vaccine. Previously, we have used the Multiple Antigen-Presenting System (MAPS) technology to generate monovalent and quadrivalent MAPS vaccines that induce functional antibodies against components.
In this work, we detail the development of several monovalent vaccines using O-specific polysaccharides (OSPs) from four dominant serotypes, 2a, 3a, and 6, and . We tested several rhizavidin (rhavi) fusion proteins and selected a -specific protein IpaB. Quadrivalent MAPS were made with Rhavi-IpaB protein and tested in rabbits for immunogenicity.
Individual MAPS vaccines generated robust, functional antibody responses against both IpaB and the individual OSP component. Antibodies to IpaB were effective across serotypes. We also demonstrate that the OSP antibodies generated are specific to each homologous O type by performing ELISA and bactericidal assays. We combined the components of each MAPS vaccine to formulate a quadrivalent MAPS vaccine which elicited similar antibody and bactericidal responses compared to their monovalent counterparts. Finally, we show that the quadrivalent MAPS immune sera are functional against several clinical isolates of the serotypes used in the vaccine.
This quadrivalent MAPS vaccine is immunogenicity and warrants further study.
志贺氏菌病是全球腹泻死亡的主要原因，在低收入和中等收入国家对5岁以下儿童尤其危险。此外，抗生素耐药性的增加凸显了有效疫苗的必要性。此前，我们已使用多抗原呈递系统（MAPS）技术来生产单价和四价MAPS疫苗，这些疫苗可诱导针对各组分的功能性抗体。
在这项工作中，我们详细阐述了几种单价疫苗的研发过程，这些疫苗使用了来自四种主要血清型（2a、3a、6和……）的O特异性多糖（OSP）。我们测试了几种根霉抗生物素蛋白（rhavi）融合蛋白，并选择了一种……特异性蛋白IpaB。用Rhavi-IpaB蛋白制备四价MAPS，并在兔子身上测试其免疫原性。
单个MAPS疫苗产生了针对IpaB和单个OSP组分的强大功能性抗体反应。针对IpaB的抗体在各血清型中均有效。我们还通过进行ELISA和杀菌试验证明，所产生的OSP抗体对每种同源O型具有特异性。我们将每种MAPS疫苗的组分组合起来，制成一种四价MAPS疫苗，与单价疫苗相比，该疫苗引发了相似的抗体和杀菌反应。最后，我们表明四价MAPS免疫血清对疫苗中使用的几种血清型临床分离株具有功能性。
这种四价MAPS疫苗具有免疫原性，值得进一步研究。
