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Infection and Immunity, March 2001, p. 1593-1598, Vol. 69, No. 3
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.3.1593-1598.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Use of a Whole Genome Approach To Identify Vaccine Molecules Affording Protection against Streptococcus pneumoniae Infection

Theresa M. Wizemann,1,dagger Jon H. Heinrichs,1 John E. Adamou,1 Alice L. Erwin,1,Dagger Charles Kunsch,2,§ Gil H. Choi,2 Steven C. Barash,2 Craig A. Rosen,2 H. Robert Masure,3,|| Elaine Tuomanen,3 Anthony Gayle,1 Yambasu A. Brewah,1 William Walsh,1 Philip Barren,1 Raju Lathigra,1 Mark Hanson,1 Solomon Langermann,1 Syd Johnson,1 and Scott Koenig1,*

MedImmune, Inc., Gaithersburg, Maryland 208781; Human Genome Sciences, Inc., Rockville, Maryland 208502; and St. Jude Children's Research Hospital, Memphis, Tennessee 381053

Received 16 October 2000/Returned for modification 29 November 2000/Accepted 12 December 2000

Microbial targets for protective humoral immunity are typically surface-localized proteins and contain common sequence motifs related to their secretion or surface binding. Exploiting the whole genome sequence of the human bacterial pathogen Streptococcus pneumoniae, we identified 130 open reading frames encoding proteins with secretion motifs or similarity to predicted virulence factors. Mice were immunized with 108 of these proteins, and 6 conferred protection against disseminated S. pneumoniae infection. Flow cytometry confirmed the surface localization of several of these targets. Each of the six protective antigens showed broad strain distribution and immunogenicity during human infection. Our results validate the use of a genomic approach for the identification of novel microbial targets that elicit a protective immune response. These new antigens may play a role in the development of improved vaccines against S. pneumoniae.

* Corresponding author. Mailing address: MedImmune, Inc., 35 W. Watkins Mill Rd., Gaithersburg, MD 20878. Phone: (301) 417-0770. Fax: (301) 527-4200. E-mail: koenigs{at}medimmune.com.

dagger Present address: The National Academies, Institute of Medicine, Washington, DC 20418.

Dagger Present address: PathoGenesis Corp., Seattle, WA 98119.

§ Present address: AtheroGenics, Inc., Alpharetta, GA 30004.

|| Present address: Genomic Search Engines (GENSE), Leawood, KS 66211.

Infection and Immunity, March 2001, p. 1593-1598, Vol. 69, No. 3
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.3.1593-1598.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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