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Infection and Immunity, August 2009, p. 3374-3379, Vol. 77, No. 8
0019-9567/09/$08.00+0     doi:10.1128/IAI.00319-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Identification of a Simple Chemical Structure Associated with Protective Human Antibodies against Multiple Pneumococcal Serogroups{triangledown}

Saeyoung Park,1 Archana R. Parameswar,2 Alexei V. Demchenko,2 and Moon H. Nahm1*

University of Alabama at Birmingham, Birmingham, Alabama 35294,1 University of Missouri-St. Louis, St. Louis, Missouri 631212

Received 19 March 2009/ Returned for modification 30 April 2009/ Accepted 11 May 2009

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){alpha}-D-Glcp(1->3){alpha}-L-Rhap(1->3)Rib-ol and {alpha}-D-Glcp(1->3){alpha}-L-Rhap(1->3)Rib-ol but did not bind {alpha}-L-Rhap(1->3)Rib-ol. The critical epitope {alpha}-D-Glcp(1->3){alpha}-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.

* Corresponding author. Mailing address: University of Alabama at Birmingham, BBRB 614, 1530 Third Avenue South, Birmingham, AL 35294-2170. Phone: (205) 934-0163. Fax: (205) 975-2149. E-mail: nahm{at}uab.edu

{triangledown} Published ahead of print on 18 May 2009.

Editor: A. Camilli

Infection and Immunity, August 2009, p. 3374-3379, Vol. 77, No. 8
0019-9567/09/$08.00+0     doi:10.1128/IAI.00319-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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