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Trypanosoma brucei

Table of Contents
  1. General Information
    1. NCBI Taxonomy ID
    2. Disease
    3. Introduction
    4. Microbial Pathogenesis
  2. Vaccine Related Pathogen Genes
    1. MAPP15 (Protective antigen)
    2. TSA (Protective antigen)
  3. Vaccine Information
    1. T. brucei DNA Vaccine encoding TSA protein
    2. T. brucei Subunit p15 Protein Vaccine
  4. References
I. General Information
1. NCBI Taxonomy ID:
5691
2. Disease:
African trypanosomiasis (African Sleeping Sickness)
3. Introduction
Trypanosomes are hemoflagellated protozoan parasites causing African sleeping sickness in humans and nagana in animals in Africa. African sleeping sickness is caused by the species Trypanosoma brucei. The incidence of disease in humans has increased 100-fold in the past 40 years, where about 55 million people and 25 million cattle have been estimated to be at risk of contracting African sleeping sickness or nagana. A total of 500,000 people estimated to be infected per year with 60,000 annual deaths. Treatment of African sleeping sickness has not advanced greatly in the last 50 years and is often highly toxic. Trypanosomiasis control programs aimed at eradication of the most common vector, the tsetse fly, though adequate if well managed, have not been fully effective (Rasooly and Balaban, 2004).
4. Microbial Pathogenesis
These obligate parasites have two hosts - an insect vector and mammalian host. Because of the large difference between these hosts the trypanosome undergoes complex changes during its life cycle to facilitate its survival in the insect gut and the mammalian bloodstream. It also features a unique and notable variable surface glycoprotein (VSG) coat in order to avoid the host's immune system (Wiki: T. brucei).
1. MAPP15
  • Gene Name : MAPP15
  • VO ID : VO_0011334
  • NCBI Protein GI : 777767
  • Taxonomy ID : 5691
  • Gene Strand (Orientation) : ?
  • Protein Name : microtubule-associated protein
  • Protein Length : 85
  • Protein Sequence : Show Sequence
    >gi|777767|gb|AAA65193.1| microtubule-associated protein [Trypanosoma brucei]
    ARATAVPKKAVAKKAAPKKTVAKKAAPKKAVAKKVAPKKAVAKKVVAKKAVAKKVVAKKVAPKKVVAKKV
    APKKVAGKKAAAKKA
  • Molecule Role : Protective antigen
  • Molecule Role Annotation : The microtubule-associate protein (MAP p15) was tested as a vaccine in mice, and tests showed that p15 (native or recombinant) generated up to 100% protection from an otherwise lethal challenge of a heterologous strain of Trypanosoma brucei (Rasooly and Balaban, 2004).
  • Related Vaccine(s): T. brucei Subunit p15 Protein Vaccine
2. TSA
  • Gene Name : TSA
  • VO ID : VO_0011338
  • NCBI Protein GI : 62175539
  • Other Database IDs : CDD:29333
  • Taxonomy ID : 5691
  • Gene Strand (Orientation) : ?
  • Protein Name : trans-sialidase
  • Protein Length : 771
  • Protein Note : Sialidases or neuraminidases function to bind and hydrolyze terminal sialic acid residues from various glycoconjugates as well as playing roles in pathogenesis, bacterial nutrition and cellular interactions. They have a six-bladed, beta-propeller fold...; cd00260
  • Protein Sequence : Show Sequence
    >gi|62175539|gb|AAX69677.1| trans-sialidase [Trypanosoma brucei]
    MEELHQQMRMPISRLLLIFTAVCHCCALTSKAAGKGTTREAFLSGGAWALRKKLSEKDGEVWWWQDGPNW
    KDKYDKEWERWFKEEKGPWGGSEKRSEWFARMTGGYITLGKTKILSSAIEGSDKVERTVHSFRIPSFVEV
    DGVLMGIGDARYLTSTDYFFTDTVAKYSADGGKTWKTEVIIENGRVDPTYSRVVDPTVVAKADSVFVLVA
    RYNVTKGYWHNENNAAGIADWEPFMYKGVVTKGADGKTSDVRISWTKTPLKPLYDFTVAGSKGTQFIGGA
    GNGVVTLNGTILFPVQARNEDNAVVSMVMYSVDDGVSWHFARGETALLTSEASLTEWNGKLLMSARTDTS
    GVNVEGGFRKVFESNNLGATWEESLGTISRVIGNSPDRTKPSPTANYPGSSGALITVTLGDVPVMLITHP
    KNTKGAWSRDRLQLWMTDGNRMWLVGQISEGDDNSAYSSLLLARDGLLYCLHEQNIDEVYGLHLVHLVDE
    LEKVNATVRKWKAQDALLAGLCSSSRKKNDPTCSGVPTDGLVGLLAGPVGASVWADVYDCVNASISDGVK
    VSEGVQLGGKRNSRVLWPVSEQGQDQRYYFANTHFTLLATVRFAGEPKAEAPLMGFSNAEGKTSETLSLT
    VGGKKWVLTYGSVRKEGPTTSMDWNQTHQIALTLRDGKVDAHVNGELIIKEVSVGASESSAHLHLSHFFI
    GAPVNDSGEGGNNVIVRNVLLYNRKLDEDELQLLYSNREKIQPVVSAVGIPEGMSAPRLCCLLILMYVLA
    I
  • Molecule Role : Protective antigen
  • Molecule Role Annotation : BALB-c mice immunized intramuscularly with a single dose (100 microg) of a plasmid DNA encoding the 5'-terminal region of the trans-sialidase (nTSA) gene of T. brucei brucei are able to produce IgG antibodies that bind to the bloodstream form of T. brucei-protein extract and recognize the recombinant nTSA protein, expressed in Escherichia coli. Furthermore, this DNA vaccination process was able to protect 60% of mice submitted to a challenge assay with the infective form of T. brucei brucei parasites (Silva et al., 2009).
  • Related Vaccine(s): T. brucei DNA Vaccine encoding TSA protein
III. Vaccine Information
1. T. brucei DNA Vaccine encoding TSA protein
a. Vaccine Ontology ID:
VO_0011491
b. Type:
DNA vaccine
c. Status:
Research
d. Gene Engineering of TSA
  • Type: DNA vaccine construction
  • Description:
  • Detailed Gene Information: Click here.
e. Vector:
pVAX1 (Silva et al., 2009)
f. Immunization Route
Intramuscular injection (i.m.)
g. Mouse Response
  • Host Strain: BALB-c
  • Vaccination Protocol: Mice were immunized by injecting 100 μg (200 μl) of plasmid DNA encoding nTSA gene by intramuscular route. As a control groups, five mice were injected with 100 μg of plasmid pVAX1LacZ (Invitrogen—USA) and with 200 μl of PBS by the same route (Silva et al., 2009).
  • Challenge Protocol: After 175 days of immunization, mice in vaccinated and control groups were submitted to the challenge assay, performed by intraperitoneal injection of 500 parasites (T. b. brucei GVR 35 1.5) per animal. The period of survival, defined as the number of days after infection that the infected animals remain alive, was evaluated (Silva et al., 2009).
  • Efficacy: The DNA vaccination process was able to protect 60% of mice submitted to a challenge assay with the infective form of T. brucei brucei parasites (Silva et al., 2009).
2. T. brucei Subunit p15 Protein Vaccine
a. Vaccine Ontology ID:
VO_0011492
b. Type:
Subunit vaccine
c. Status:
Research
d. Gene Engineering of MAPP15
  • Type: Recombinant protein preparation
  • Description:
  • Detailed Gene Information: Click here.
e. Adjuvant: complete Freunds adjuvant
f. Adjuvant: incomplete Freunds adjuvant
g. Immunization Route
Subcutaneous
h. Mouse Response
  • Host Strain: Swiss
  • Vaccination Protocol: Swiss male mice were injected three times subcutaneously on days 1, 7 and 21 with the antigen. Antigen contained 10 μg of native p15 isolated from T. brucei brucei KETRI 2693, recombinant p15 purified from Ad-p15 infected HEK293 cells, partially purified subpellicular microtubules as a positive control (subpellicular fraction >30 kDa), or with PIPES buffer used to purify p15 as a negative control. Vaccinations included complete Freund’s adjuvant on first injection and incomplete Freund’s adjuvant on second and third injections. To test the protective potential of the recombinant viral vaccine, mice were injected intramuscularly (on days 1, 7 and 21) with 2×109 Ad-p15 virus particles or with control Ad-lacZ (Rasooly and Balaban, 2004).
  • Challenge Protocol: Animals were challenged intraperitoneally on day 31 with 500 T. brucei brucei strain SB1 (Rasooly and Balaban, 2004).
  • Efficacy: Vaccination of mice with p15 (native or recombinant) generated up to 100% protection from an otherwise lethal challenge of a heterologous strain of Trypanosoma brucei (Rasooly and Balaban, 2004).
IV. References
1. Rasooly and Balaban, 2004: Rasooly R, Balaban N. Trypanosome microtubule-associated protein p15 as a vaccine for the prevention of African sleeping sickness. Vaccine. 2004; 22(8); 1007-1015. [PubMed: 15161078].
2. Silva et al., 2009: Silva MS, Prazeres DM, Lança A, Atouguia J, Monteiro GA. Trans-sialidase from Trypanosoma brucei as a potential target for DNA vaccine development against African trypanosomiasis. Parasitology research. 2009; 105(5); 1223-1229. [PubMed: 19582478].
3. Wiki: T. brucei: Wiki: Trypanosoma brucei [http://en.wikipedia.org/wiki/T._brucei]