Effective vaccination of mice against<i>Mycobacterium leprae</i>with density-gradient subfractions of soluble<i>M. leprae</i>proteins: clues to effective protein epitopes

Gelber, Robert H.; Hunter, S W; Murray, L P; Siu, Patricia; Tsang, M; Brennan, Patrick J.

doi:10.5935/0305-7518.19940017

Cited by 4 publications

(5 citation statements)

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“…The 10kDa, 65kDa-1 and 28kDa SodA proteins were shown to induce some, albeit limited, protection, whereas the 18 kDa and 35 kDa proteins failed to do so (Gelber et aL, 1994). As indicated above, while some antigens may have a better intrinsic protective potential than others, subunit vaccines may not trigger an immune response that results in a long-term high degree of protection.…”

Section: In Vivo Immunological Protectionmentioning

confidence: 98%

Immunological and functional characterization of Mycobacterium leprae protein antigens: an overview

Thole

Wieles

Clark‐Curtiss

et al. 1995

Molecular Microbiology

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Section: In Vivo Immunological Protectionmentioning

confidence: 98%

Immunological and functional characterization of Mycobacterium leprae protein antigens: an overview

Thole

Wieles

Clark‐Curtiss

et al. 1995

Molecular Microbiology

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“…This has impaired the ability to produce antigens for research purposes, and until recently, studies of antigen-specific immune responses during the course of the disease have been limited to using crude bacterial extracts or a few single M. leprae antigens purified from animal extracts (10,18,27). Partial vaccination against M. leprae can be achieved with other mycobacteria, but a defined subunit vaccine for leprosy is lacking (7,14).…”

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confidence: 99%

Antigen-Specific T-Cell Responses of Leprosy Patients

Duthie

Goto

Ireton

et al. 2008

Clin Vaccine Immunol

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The identification of human T-cell antigens of Mycobacterium leprae could improve treatment and help to disrupt the transmission of leprosy by directing diagnosis and vaccine programs. This study screened a panel of M. leprae recombinant proteins for T-cell recall responses, measured by gamma interferon (IFN-␥) production, among leprosy patients. After initial studies using peripheral blood mononuclear cells from leprosy patients, we transitioned our studies to simple whole-blood assays (WBA), which are more applicable in field or clinical settings. T-cell responses generated in WBA using blood from individuals in Goiânia, Brazil, demonstrated that several M. leprae antigens (ML0276, ML0840, ML1623, ML2044, and 46f) elicited >0.5 IU/ml IFN-␥, and these proteins were classified as immunogenic and leprosy specific. Several of these individual antigens were recognized by cells from >60% of Brazilian paucibacillary (PB) leprosy patients, and ML0276, ML0840, ML1623, and 46f complemented each other such that 82% of PB patients had strong (>1.25 IU/ml IFN-␥) responses to at least one of these proteins. These proteins were also recognized by cells from a significant proportion of the household contacts of multibacillary leprosy patients, but in contrast, few responses were observed in active tuberculosis patients or healthy control groups from areas of endemicity. Our results indicate several potential candidate antigens which may be useful for either leprosy diagnosis or vaccination and demonstrate the utility of leprosy WBA that can be applied broadly in clinical or field settings.Leprosy is a chronic disease with a wide range of clinical outcomes. Leprosy patients are predominantly diagnosed by the appearance of disease signs, but they can also be characterized by the physical and histological attributes of skin or nerve lesions or by their immune response to crude Mycobacterium leprae antigens (25). Individuals infected with M. leprae exhibit wide-ranging immunity. One end of this immunologic spectrum comprises paucibacillary (PB) leprosy patients, who have strong cellular immunity in the form of a Th1-type response characterized by antigen-specific gamma interferon (IFN-␥) secretion. This response controls bacterial growth and limits dissemination, typically resulting in a few small and localized lesions. At the other end of the spectrum, multibacillary (MB) patients have poor cellular immunity but potent humoral immunity. Responses of MB patients do not control bacterial growth, and infection becomes systemic, typically resulting in disseminated lesions and significant nerve function impairment. Identifying antigens that are the target of the cellular immune response could direct the development of a defined leprosy vaccine.Despite vigorous efforts, conditions that permit the in vitro culture of M. leprae bacilli have not yet been identified. This has impaired the ability to produce antigens for research purposes, and until recently, studies of antigen-specific immune responses during the course of the disease hav...

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“…Thus, the identification and synthesis of these low-molecular-weight peptides should be pursued. Furthermore, in our previous studies (6)(7)(8), it was found frequently that mouse vaccination with largely proteinaceous subunits of M. leprae provided impressive protection, often with no M. leprae at all being detected in vaccinated mice upon footpad harvests following a preceding viable-M. leprae challenge. Particularly, in a previous study (8), mouse vaccination with soluble proteins of M. leprae resulted in both impressive protection and generally detection of absolutely no acid-fast bacilli at al.…”

Section: Discussionmentioning

confidence: 92%

“…In several studies, mycobacterial growth was also determined 3 months after peak multiplication was noted in the negative control, the plateau phase. It is noteworthy that in studies such as these, there is considerable (10-fold or more) variability in the number of M leprae organisms enumerated at the peak of multiplication in individual footpads of mice immunized with FIA alone (6)(7)(8)27). This is a function of several factors.…”

Section: Materuils and Methodsmentioning

confidence: 99%

Vaccination with pure Mycobacterium leprae proteins inhibits M. leprae multiplication in mouse footpads

et al. 1994

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In this study, we evaluated vaccination with a number of purified, as well as recombinant, Mycobacterium leprae proteins for protective efficacy in mice. BALB/c mice were immunized intradermally with various native somatic (purified) or recombinant M. leprae proteins and their synthetic polypeptides emulsified in Freund's incomplete adjuvant. The protective efficacy of these preparations was assessed by enumeration of bacilli in the footpads of mice challenged with viable M. leprae 1 to 2 months following immunization. Protection was afforded by the purified and recombinant 10-kDa M. leprae cytoplasmic heat shock protein, the recombinant cell wall-associated 65-kDa M. leprae heat shock protein, and to a lesser extent, the purified 28-kDa M. leprae cytoplasmic protein (superoxide dismutase). Vaccination with either the purified or recombinant 35-kDa M. leprae cell membrane protein, the synthetic 27-amino-acid N-terminal peptide of the 10-kDa protein, the recombinant 18-kDa M. leprae protein, or the purified 22-kDa cell membrane protein was ineffective. When the interval between immunization and challenge was increased to 6 months, the purified 10-kDa M. leprae protein and the recombinant 65-kDa M. leprae protein lost vaccine efficacy, while a sodium dodecyl sulfate-soluble protein fraction of the M. leprae cell wall (soluble proteins), as had been found previously, continued to protect, suggesting that multiple M. leprae protein epitopes are critical for solid vaccine protection.

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Effective vaccination of mice againstMycobacterium lepraewith density-gradient subfractions of solubleM. lepraeproteins: clues to effective protein epitopes

Cited by 4 publications

References 1 publication

Immunological and functional characterization of Mycobacterium leprae protein antigens: an overview

Immunological and functional characterization of Mycobacterium leprae protein antigens: an overview

Antigen-Specific T-Cell Responses of Leprosy Patients

Vaccination with pure Mycobacterium leprae proteins inhibits M. leprae multiplication in mouse footpads

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