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Infection and Immunity, August 2003, p. 4498-4505, Vol. 71, No. 8
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.8.4498-4505.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Relative Roles of Genetic Background and Variation in PspA in the Ability of Antibodies to PspA To Protect against Capsular Type 3 and 4 Strains of Streptococcus pneumoniae

Hazeline Roche,1,{dagger} Bing Ren,1 Larry S. McDaniel,2 Anders Håkansson,1,{ddagger} and David E. Briles1*

Department of Microbiology, University of Alabama at Birmingham, Birmingham, Alabama 35294,1 Department of Microbiology, The University of Mississippi Medical Center, Jackson, Mississippi 392162

Received 16 July 2002/ Returned for modification 12 November 2002/ Accepted 27 May 2003

Pneumococcal surface protein A (PspA) is able to elicit antibodies in mice and humans that can protect mice against fatal infection with Streptococcus pneumoniae. It has been observed that immunization with a single family 1 PspA can protect mice against infections with capsular type 3 or 6B strains expressing PspA family 1 or 2. However, several studies have shown that immunity to PspA is less efficacious against several capsular type 4 strains than against strains of capsular types 3, 6A, and 6B. To determine whether the greater difficulty in protecting against capsular type 4 strains resulted from differences in their PspAs or from differences in their genetic backgrounds, we performed protection experiments using four different challenge strains: a capsular type 3 strain expressing a family 1 PspA (WU2), a capsular type 4 strain expressing a family 2 PspA (TIGR4), and genetically engineered variants of WU2 and TIGR4 expressing each other's PspAs. Prior to infection, the mice were immunized with recombinant family 1 or family 2 PspA. The results revealed that much of the difficulty in protecting against capsular type 4 strains was eliminated when mice were immunized with a homologous PspA of the same PspA family. However, regardless of which PspA the strains expressed, those on the TIGR4 background were about twice as hard to protect against as WU2 strains expressing the same PspA based on the efficacy rates seen in our experiments. These results point out the importance of including more than one PspA in any PspA vaccines developed for human use.

* Corresponding author. Mailing address: Department of Microbiology, University of Alabama at Birmingham, BBRB-658, Box 10, 845 19th St. South, Birmingham, AL 35294. Phone: (205) 934-6595. Fax: (205) 934-0605. E-mail: dbriles{at}uab.edu.

Editor: V. J. DiRita

{dagger} Present address: Genetica Inc., Cambridge, MA 02139.

{ddagger} Present address: Channing Laboratory, Brigham and Women's Hospital, Boston, MA 02115.

Infection and Immunity, August 2003, p. 4498-4505, Vol. 71, No. 8
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.8.4498-4505.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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