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Infection and Immunity, September 2002, p. 5086-5090, Vol. 70, No. 9
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.9.5086-5090.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Analysis of Serum Cross-Reactivity and Cross-Protection Elicited by Immunization with DNA Vaccines against Streptococcus pneumoniae Expressing PspA Fragments from Different Clades

Eliane N. Miyaji,1* Daniela M. Ferreira,1 Alexandre P. Y. Lopes,1 M. Cristina C. Brandileone,2 Waldely O. Dias,1 and Luciana C. C. Leite1

Centro de Biotecnologia, Instituto Butantan,1 Seção de Bacteriologia, Instituto Adolfo Lutz, São Paulo, Brazil2

Received 18 March 2002/ Returned for modification 1 May 2002/ Accepted 10 June 2002

Streptococcus pneumoniae is a major cause of disease, especially in developing countries, and cost-effective alternatives to the currently licensed vaccines are needed. We constructed DNA vaccines based on pneumococcal surface protein A (PspA), an antigen shown to induce protection against pneumococcal bacteremia. PspA fragments can be divided into three families, which can be subdivided into six clades, on the basis of PspA amino acid sequence divergence (S. K. Hollingshead, R. Becker, and D. E. Briles, Infect. Immun. 68:5889-5900, 2000). Since most clinical isolates belong to family 1 or family 2, PspA fragments from members of both of these families were analyzed. Vectors encoding the complete N-terminal regions of PspAs elicited significant humoral responses, and cross-reactivity was mainly restricted to the same family. DNA vaccines encoding fusions between PspA fragments from family 1 and family 2 were also constructed and were able to broaden the cross-reactivity, with induction of antibodies that showed reactions with members of both families. At least for the pneumococcal strains tested, the cross-reactivity of antibodies was not reflected in cross-protection. Animals immunized with DNA vaccines expressing the complete N-terminal regions of PspA fragments were protected only against intraperitoneal challenge with a strain expressing PspA from the same clade.

* Corresponding author. Mailing address: Centro de Biotecnologia, Instituto Butantan, Av. Vital Brasil, 1500, 05503-900, São Paulo, SP, Brazil. Phone: 55-11-3726-7222, ext. 2242. Fax: 55-11-3726-9150. E-mail: enmiyaji{at}uol.com.br.

Editor: E. I. Tuomanen

Infection and Immunity, September 2002, p. 5086-5090, Vol. 70, No. 9
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.9.5086-5090.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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