Proteins of the Rpf family: immune cell reactivity and vaccination efficacy against tuberculosis in mice.
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.
Yeremeev
Vladimir V
VV
Central Institute for Tuberculosis, Russian Academy of Medical Sciences, Moscow, Russia.
Kondratieva
Tatiana K
TK
Rubakova
Elvira I
EI
Petrovskaya
Svetlana N
SN
Kazarian
Konstantin A
KA
Telkov
Miroslav V
MV
Biketov
Sergej F
SF
Kaprelyants
Arseny S
AS
Apt
Alexander S
AS
D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D005260:Female; D066298:In Vitro Techniques; D008168:Lung / Q000276:immunology / Q000382:microbiology; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D009169:Mycobacterium tuberculosis / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification; D013154:Spleen / Q000276:immunology / Q000382:microbiology; D013601:T-Lymphocytes / Q000276:immunology; D014376:Tuberculosis / Q000276:immunology* / Q000382:microbiology / Q000517:prevention & control*; D032581:Tuberculosis Vaccines / Q000235:genetics / Q000276:immunology / Q000494:pharmacology*; D022223:Vaccines, Subunit / Q000235:genetics / Q000276:immunology / Q000494:pharmacology
D000907:Antibodies, Bacterial; D001426:Bacterial Proteins; D016207:Cytokines; D032581:Tuberculosis Vaccines; D022223:Vaccines, Subunit; C113704:resuscitation-promoting factor, bacteria