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Infection and Immunity, August 2003, p. 4789-4794, Vol. 71, No. 8
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.8.4789-4794.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Proteins of the Rpf Family: Immune Cell Reactivity and Vaccination Efficacy against Tuberculosis in Mice

Vladimir V. Yeremeev,1 Tatiana K. Kondratieva,1 Elvira I. Rubakova,1 Svetlana N. Petrovskaya,1 Konstantin A. Kazarian,2 Miroslav V. Telkov,2 Sergej F. Biketov,3 Arseny S. Kaprelyants,2 and Alexander S. Apt1*

Central Institute for Tuberculosis, Russian Academy of Medical Sciences,1 Bakh Institute of Biochemistry, Russian Academy of Sciences, Moscow,2 State Research Centre for Applied Microbiology, Obolensk, Moscow Region, Russia3

Received 23 December 2002/ Returned for modification 24 February 2003/ Accepted 6 May 2003

It was shown recently that Mycobacterium tuberculosis expresses five proteins that are homologous to Rpf (resuscitation promoting factor), which is secreted by growing cells of Micrococcus luteus. Rpf is required to resuscitate the growth of dormant Micrococcus luteus organisms, and its homologues may be involved in mycobacterial reactivation. Mycobacterial Rpf-like products are secreted proteins, which makes them candidates for recognition by the host immune system and anti-Rpf immune responses potentially protective against reactivated tuberculosis. Here we report that the Rpf protein itself and four out of five of its mycobacterial homologues, which were administered as subunit vaccines to C57BL/6 mice, are highly immunogenic. Rpf-like proteins elicit immunoglobulin G1 (IgG1) and IgG2a responses and T-cell proliferation and stimulate production of gamma interferon, interleukin-10 (IL-10), and IL-12 but not IL-4 or IL-5. Both humoral and T-cell responses against these antigens show a high degree of cross-reactivity. Vaccination of mice with Rpf-like proteins results in a significant level of protection against a subsequent high-dose challenge with virulent M. tuberculosis H37Rv, both in terms of survival times and mycobacterial multiplication in lungs and spleens.

* Corresponding author. Mailing address: Laboratory for Immunogenetics, Central Institute for Tuberculosis, Yauza Alley 2, Moscow 107564, Russia. Phone: 7 095 268 78 10. Fax: 7 095 963 80 00. E-mail: asapt{at}aha.ru.

Editor: S. H. E. Kaufmann

Infection and Immunity, August 2003, p. 4789-4794, Vol. 71, No. 8
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.8.4789-4794.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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