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Proc Natl Acad Sci U S A. 2015 Mar 10;112(10):E1143-51. doi: 10.1073/pnas.1425005112. Epub 2015 Feb 19.

Conjugate-like immunogens produced as protein capsular matrix vaccines.

Author information

1
Matrivax Research & Development Corporation, Boston, MA 02118; and.
2
Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115 jmekalanos@hms.harvard.edu.

Abstract

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.

KEYWORDS:

T-independent antigens; protein capsular complexes; virtual polysaccharide conjugates

PMID:
25699685
PMCID:
PMC4364189
DOI:
10.1073/pnas.1425005112
[Indexed for MEDLINE]
Free PMC Article

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