Thanawastien Ann, Cartee Robert T, Griffin Thomas J, Killeen Kevin P, Mekalanos John J
Matrivax Research & Development Corporation, Boston, MA 02118; and.
Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115
Proc Natl Acad Sci U S A. 2015 Mar 10;112(10):E1143-51. doi: 10.1073/pnas.1425005112. Epub 2015 Feb 19.
Capsular polysaccharides are the primary antigenic components involved in protective immunity against encapsulated bacterial pathogens. Although immunization of adolescents and adults with polysaccharide antigens has reduced pathogen disease burden, pure polysaccharide vaccines have proved ineffective at conferring protective immunity to infants and the elderly, age cohorts that are deficient in their adaptive immune responses to such antigens. However, T-cell-independent polysaccharide antigens can be converted into more potent immunogens by chemically coupling to a "carrier protein" antigen. Such "conjugate vaccines" efficiently induce antibody avidity maturation, isotype switching, and immunological memory in immunized neonates. These immune responses have been attributed to T-cell recognition of peptides derived from the coupled carrier protein. The covalent attachment of polysaccharide antigens to the carrier protein is thought to be imperative to the immunological properties of conjugate vaccines. Here we provide evidence that covalent attachment to carrier proteins is not required for conversion of T-independent antigens into T-dependent immunogens. Simple entrapment of polysaccharides or a d-amino acid polymer antigen in a cross-linked protein matrix was shown to be sufficient to produce potent immunogens that possess the key characteristics of conventional conjugate vaccines. The versatility and ease of manufacture of these antigen preparations, termed protein capsular matrix vaccines (PCMVs), will likely provide improvements in the manufacture of vaccines designed to protect against encapsulated microorganisms. This in turn could improve the availability of such vaccines to the developing world, which has shown only a limited capacity to afford the cost of conventional conjugate vaccines.
荚膜多糖是参与针对有荚膜细菌病原体的保护性免疫的主要抗原成分。尽管用多糖抗原对青少年和成年人进行免疫接种已降低了病原体疾病负担，但纯多糖疫苗已被证明对婴儿和老年人无效，这两个年龄组对这类抗原的适应性免疫反应不足。然而，通过化学偶联到“载体蛋白”抗原上，非T细胞依赖性多糖抗原可以转化为更强效的免疫原。这种“结合疫苗”能在免疫的新生儿中有效诱导抗体亲和力成熟、抗体亚型转换和免疫记忆。这些免疫反应归因于T细胞对来自偶联载体蛋白的肽段的识别。多糖抗原与载体蛋白的共价连接被认为对结合疫苗的免疫特性至关重要。在此，我们提供证据表明，非T细胞依赖性抗原转化为T细胞依赖性免疫原并不需要与载体蛋白共价连接。将多糖或d -氨基酸聚合物抗原简单包埋在交联蛋白基质中已被证明足以产生具有传统结合疫苗关键特性的强效免疫原。这些抗原制剂被称为蛋白荚膜基质疫苗（PCMV），其多功能性和易于制造的特点可能会改进针对有荚膜微生物的疫苗生产。这反过来可能会提高这类疫苗在发展中世界的可及性，因为发展中世界支付传统结合疫苗费用的能力有限。
