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Infection and Immunity, February 2001, p. 949-958, Vol. 69, No. 2
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.2.949-958.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Identification and Characterization of a Novel Family of Pneumococcal Proteins That Are Protective against Sepsis

John E. Adamou,1,* Jon H. Heinrichs,1 Alice L. Erwin,1,dagger William Walsh,1 Tony Gayle,1 Melissa Dormitzer,1 Ron Dagan,2 Yambasu A. Brewah,1 Philip Barren,1 Raju Lathigra,1 Solomon Langermann,1 Scott Koenig,1 and Syd Johnson1

MedImmune, Inc., Gaithersburg, Maryland 20878,1 and Pediatric Infectious Disease Unit, Soroka University Medical Center and the Faculty of Health Sciences, Ben-Gurion University, Beer-Sheva 84101, Israel2

Received 24 August 2000/Returned for modification 30 October 2000/Accepted 15 November 2000

Four pneumococcal genes (phtA, phtB, phtD, and phtE) encoding a novel family of homologous proteins (32 to 87% identity) were identified from the Streptococcus pneumoniae genomic sequence. These open reading frames were selected as potential vaccine candidates based upon their possession of hydrophobic leader sequences which presumably target these proteins to the bacterial cell surface. Analysis of the deduced amino acid sequences of these gene products revealed the presence of a histidine triad motif (HxxHxH), termed Pht (pneumococcal histidine triad) that is conserved and repeated several times in each of the four proteins. The four pht genes (phtA, phtB, phtD, and a truncated version of phtE) were expressed in Escherichia coli. A flow cytometry-based assay confirmed that PhtA, PhtB, PhtD and, to a lesser extent, PhtE were detectable on the surface of intact bacteria. Recombinant PhtA, PhtB, and PhtD elicited protection against certain pneumococcal capsular types in a mouse model of systemic disease. These novel pneumococcal antigens may serve as effective vaccines against the most prevalent pneumococcal serotypes.

* Corresponding author. Mailing address: MedImmune, Inc., 25 W. Watkins Mill Rd., Gaithersburg, MD 20878. Phone: (301) 527-4309. Fax: (301) 527-4214. E-mail: adamouje{at}medimmune.com.

dagger Present address: Pathogenesis Corp., Seattle, WA 98119.

Infection and Immunity, February 2001, p. 949-958, Vol. 69, No. 2
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.2.949-958.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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