Park S, Parameswar AR, Demchenko AV, Nahm MH Identification of a simple chemical structure associated with protective human antibodies against multiple pneumococcal serogroups Infection and Immunity77(8) (2009)
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NCBI PubMed ID:19451241 Publication DOI:10.1128/IAI.00319-09 Journal NLM ID:0246127 Publisher: American Society for Microbiology Correspondence: nahmuab.edu Institutions: University of Alabama at Birmingham, 35294-2170, USA
Streptococcus pneumoniae, a major human pathogen, expresses at least 91 serologically distinct carbohydrate capsules. Since pneumococcal vaccines are designed to elicit antibodies against many different capsular polysaccharides (PSs), it is important to identify the epitopes involved in eliciting anti-capsular PS antibodies. We investigated the epitopes recognized by Dob1, which is a hybridoma-secreting human immunoglobulin G2 antibody to the PS of serotype 6B (Y. Sun et al., Infect. Immun. 67:1172-1179, 1999). We found that Dob1 bound synthetic capsular carbohydrates Gal(1→3)α-D-Glcp(1→3)α-L-Rhap(1→3)Rib-ol and α-D-Glcp(1→3)α-L-Rhap(1→3)Rib-ol but did not bind α-L-Rhap(1→3)Rib-ol. The critical epitope α-D-Glcp(1→3)α-L-Rhap is found in the capsular PSs of serotypes 6A, 6B, 6C, and 19A but not in the 19F PS. Consistent with this observation, Dob1 bound to the PSs of serotypes 6A, 6B, 6C, and 19A but did not bind the 19F PS and 23 additional unrelated pneumococcal capsular PSs. Also, Dob1 could opsonize pneumococci expressing serotypes 6A, 6B, 6C, and 19A but did not opsonize 19F pneumococci. In addition, ca. 7% of immune sera (12 of 175 sera) had significant amounts of Dob1-like antibodies, i.e., reacted with 6B and 19A PSs, but not with 19F PS. Humans can produce antibodies to the Dob1 epitope and the antibodies to that epitope cross-react with the four serotypes 6A, 6B, 6C, and 19A that belong to different serogroups. This epitope may be useful for producing a totally synthetic, simple chemical structure that is capable of generating protective antibodies to multiple pneumococcal serogroups.
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