Immunization of guinea pigs with recombinant TmpB antigen induces protection against challenge infection with Treponema pallidum Nichols

Wicher, Konrad; Schouls, Leo M.; Wicher, Victoria; Embden, J. D. A. Van; Nakeeb, Shaheen

doi:10.1128/iai.59.12.4343-4348.1991

Cited by 25 publications

(5 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This modest degree of protective immunity probably reflects differences in immunization protocols. It is also important to note that comparable levels of partial protection have previously been observed following immunization with T. pallidum proteins which are known to be intracellular (13,18,65), most likely reflecting a cellular component in the protective immune response.…”

Section: Resultsmentioning

confidence: 66%

Membrane Topology and Cellular Location of theTreponema pallidumGlycerophosphodiester Phosphodiesterase (GlpQ) Ortholog

Shevchenko¹,

Sellati²,

Cox

et al. 1999

Infect Immun

View full text Add to dashboard Cite

Recent reports that isolated Treponema pallidum outer membranes contain an ortholog for glycerophosphodiester phosphodiesterase (GlpQ) (, Infect. Immun. 65:4179-4189, 1997) and that this protein is a potential opsonic target for T. pallidum (C. E. Stebeck, J. M. Shaffer, T. W. Arroll, S. A. Lukehart, and W. C. Van Voorhis, FEMS Microbiol. Lett. 154:303-310, 1997) prompted a more detailed investigation of its physicochemical properties and cellular location. [ 14 C]palmitate radiolabeling studies of a GlpQ-alkaline phosphatase fusion expressed in Escherichia coli confirmed the prediction from DNA sequencing that the protein is lipid modified. Studies using Triton X-114 phase partitioning revealed that the protein's amphiphilicity is due to lipid modification and that a substantial portion of the polypeptide is associated with the T. pallidum peptidoglycan sacculus. Three different approaches, i.e., (i) proteinase K treatment of intact treponemes, (ii) indirect immunofluorescence analysis of treponemes encapsulated in agarose beads, and (iii) opsonophagocytosis of treponemes incubated with antiserum against recombinant GlpQ by rabbit peritoneal macrophages, confirmed that GlpQ is entirely subsurface in T. pallidum. Moreover, rabbits hyperimmunized with GlpQ were not protected against intradermal challenge with virulent treponemes. Circular dichroism spectroscopy confirmed that the recombinant form of the polypeptide lacked discernible evidence of denaturation. Finally, GlpQ was not radiolabeled when T. pallidum outer membranes were incubated with 3-(trifluoromethyl)-3-(m-[ 125 I]iodophenyl)-diazarene, a photoactivatable, lipophilic probe which promiscuously labels both proteins and lipids within phospholipid bilayers. Taken as a whole, these studies indicate that the T. pallidum GlpQ ortholog is a periplasmic protein associated predominantly with the spirochete's peptidoglycan-cytoplasmic membrane complex. MATERIALS AND METHODSBacterial strains. T. pallidum (Nichols) was propagated by intratesticular inoculation of adult New Zealand White rabbits as previously described (52). Spirochetes were separated from testicular tissue debris by low-speed centrifugation (350 ϫ g for 10 min) and, when necessary, purified by Percoll density gradient centrifugation (30). For opsonophagocytosis assays, organisms were extracted from infected testes in medium 199 (M199) (Mediatech, Herndon, Va.) supplemented with 20% heat-inactivated fetal bovine serum (HIFBS) (heated for 30 min at 56°C) (Mediatech) and gassed with 3% O 2 -5% CO 2 overnight at 37°C. Spirochetes were enumerated by dark-field microscopy with a Petroff-Hausser counting chamber (Hausser Scientific Company, Horsham, Pa.). E. coli

show abstract

Section: Resultsmentioning

confidence: 66%

Membrane Topology and Cellular Location of theTreponema pallidumGlycerophosphodiester Phosphodiesterase (GlpQ) Ortholog

Shevchenko¹,

Sellati²,

Cox

et al. 1999

Infect Immun

View full text Add to dashboard Cite

show abstract

“…Immunization with TmpA, TmpB, and TmpC. Schouls and colleagues (190,240,241) have investigated the immunogenicity of three T. pallidum membrane-associated polypeptides in the guinea pig model. When crude fractions of TmpA and TmpB or purified TmpC were used for immunization of inbred strain 2 guinea pigs, no protection was observed (241).…”

Section: T Pauidum Polypeptides As Vaccinogensmentioning

confidence: 99%

Polypeptides of Treponema pallidum: progress toward understanding their structural, functional, and immunologic roles. Treponema Pallidum Polypeptide Research Group.

Norris

1993

Microbiological Reviews

116

View full text Add to dashboard Cite

“…Previous attempts at vaccine development for syphilis have achieved varying degrees of success 16 . Immunization of rabbits, the optimal animal model that recapitulates the multiple stages and chronicity of human syphilis, with a selection of individual recombinant proteins has elicited at best partial protection 17 18 19 20 21 22 23 24 25 26 27 28 29 30 . More promising protection results have been achieved using attenuated whole-cell T. pallidum preparations 31 32 33 .…”

mentioning

confidence: 99%

A defined syphilis vaccine candidate inhibits dissemination of Treponema pallidum subspecies pallidum

et al. 2017

View full text Add to dashboard Cite

Syphilis is a prominent disease in low- and middle-income countries, and a re-emerging public health threat in high-income countries. Syphilis elimination will require development of an effective vaccine that has thus far remained elusive. Here we assess the vaccine potential of Tp0751, a vascular adhesin from the causative agent of syphilis, Treponema pallidum subsp. pallidum. Tp0751-immunized animals exhibit a significantly reduced bacterial organ burden upon T. pallidum challenge compared with unimmunized animals. Introduction of lymph nodes from Tp0751-immunized, T. pallidum-challenged animals to naive animals fails to induce infection, confirming sterile protection. These findings provide evidence that Tp0751 is a promising syphilis vaccine candidate.

show abstract

Immunization of guinea pigs with recombinant TmpB antigen induces protection against challenge infection with Treponema pallidum Nichols

Cited by 25 publications

References 21 publications

Membrane Topology and Cellular Location of theTreponema pallidumGlycerophosphodiester Phosphodiesterase (GlpQ) Ortholog

Membrane Topology and Cellular Location of theTreponema pallidumGlycerophosphodiester Phosphodiesterase (GlpQ) Ortholog

Polypeptides of Treponema pallidum: progress toward understanding their structural, functional, and immunologic roles. Treponema Pallidum Polypeptide Research Group.

A defined syphilis vaccine candidate inhibits dissemination of Treponema pallidum subspecies pallidum

Contact Info

Product

Resources

About