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Chembiochem 2017 Apr 18;18(8):799-815

Conjugate vaccines from bacterial antigens by squaric acid chemistry: a closer look.

Xu P, Kelly M, Vann WF, Qadri F, Ryan ET, Kovac P

Abstract

By using O-SP-core (O-SPcNH2 ) polysaccharide, isolated from Vibrio cholera O1 lipopolysaccharide (LPS) and related synthetic substances, a detailed study of factors that affect conjugation of bacterial polysaccharides to protein carriers through squaric acid chemistry to form conjugate vaccines has been carried out. Several previously unrecognized processes that take place during the squarate labeling of the O-SPcNH2 and subsequent conjugation of the formed squarate (O-SPcNH-SqOMe) have been identified. The efficiency of conjugation at pH 8.5, 9.0, and 9.5 to bovine serum albumin (BSA) and to the recombinant tetanus toxin fragment C (rTT-Hc) has been determined. The study led to a protocol for more efficient labeling of O-SPcNH2 antigen with the methyl squarate group, to yield a higher-quality, more potent squarate conjugation reagent. Its use resulted in about twofold increases in conjugation efficiency (from 23-26 % on BSA to 51 % on BSA and 55 % on rTT-Hc). The spent conjugation reagent could be recovered and regenerated by treatment with MeI in the absence of additional base. The immunological properties of the experimental vaccine made from the regenerated conjugation reagent were comparable with those of the immunogen made from the parent O-SPcNH-SqOMe.


Category: Journal Article
PubMed ID: #28182850 DOI: 10.1002/cbic.201600699
Includes FDA Authors from Scientific Area(s): Biologics
Entry Created: 2017-05-23 Entry Last Modified: 2019-06-09
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