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Vaccine Comparison

L. donovani Beta-tubulin Protein Vaccine L. donovani DNA Vaccine encoding KMP-11 L. donovani DNA Vaccine encoding NH36 Protein L. donovani gp63 Protein Vaccine L. donovani GRP-78 Protein Vaccine L. donovani HASPB1 Protein Vaccine L. donovani Hsp70 Protein Vaccine L. donovani LD31 Protein Vaccine L. donovani ORFF Protein Vaccine L. donovani Recombinant LdγGCS in NIV system Vaccine Leishmania donovani cen1 mutant vaccine Leishmania vaccine using recombinant L. tarentolae strain expressing A2 antigen SL3261-L. donovani
Vaccine Information Vaccine Information Vaccine Information Vaccine Information Vaccine Information Vaccine Information Vaccine Information Vaccine Information Vaccine Information Vaccine Information Vaccine Information Vaccine Information Vaccine Information
  • Vaccine Ontology ID: VO_0004023
  • Type: Subunit vaccine
  • Status: Research
  • Beta-tubulin gene engineering:
    • Type: Recombinant protein preparation
    • Detailed Gene Information: Click Here.
  • Adjuvant: cationic liposomal vaccine adjuvant DDA:TDB
  • Immunization Route: Intraperitoneal injection (i.p.)
  • Vaccine Ontology ID: VO_0011530
  • Type: DNA vaccine
  • Status: Research
  • KMP-11 gene engineering:
    • Type: DNA vaccine construction
    • Description: KMP-11was cloned into a pCMV-LIC vector for DNA vaccine candidate in mice (Bhaumik et al., 2009).
    • Detailed Gene Information: Click Here.
  • Adjuvant: IL-12 vacince adjuvant
  • Vector: pCMV-LIC (Bhaumik et al., 2009).
  • Immunization Route: Subcutaneous injection
  • Vaccine Ontology ID: VO_0011542
  • Type: DNA vaccine
  • Status: Research
  • NH gene engineering:
    • Type: DNA vaccine construction
    • Detailed Gene Information: Click Here.
  • Vector: VR1012 (Aguilar-Be et al., 2005)
  • Immunization Route: Intramuscular injection (i.m.)
  • Vaccine Ontology ID: VO_0011532
  • Type: Subunit vaccine
  • Status: Research
  • mspC gene engineering:
    • Type: Recombinant protein preparation
    • Detailed Gene Information: Click Here.
  • Adjuvant: liposome-based vaccine adjuvant
  • Immunization Route: Intraperitoneal injection (i.p.)
  • Vaccine Ontology ID: VO_0004022
  • Type: Subunit vaccine
  • Status: Research
  • GRP-78 gene engineering:
    • Type: Recombinant protein preparation
    • Detailed Gene Information: Click Here.
  • Adjuvant: IL-12 vacince adjuvant
  • Immunization Route: Subcutaneous injection
  • Vaccine Ontology ID: VO_0004067
  • Type: Subunit vaccine
  • Status: Research
  • Antigen: Recombinant hydrophilic acylated surface protein B1 (HASPB1) (Stäger et al., 2000).
  • HASPB1 gene engineering:
    • Type: Recombinant protein preparation
    • Detailed Gene Information: Click Here.
  • Adjuvant: IL-12 vacince adjuvant
  • Immunization Route: Subcutaneous injection
  • Vaccine Ontology ID: VO_0004033
  • Type: Subunit vaccine
  • Status: Research
  • Antigen: LD72 (Hsp70) protein
  • hsp70 gene engineering:
    • Type: Recombinant protein preparation
    • Detailed Gene Information: Click Here.
  • Vector: Liposomes
  • Immunization Route: Intraperitoneal injection (i.p.)
  • Vaccine Ontology ID: VO_0004179
  • Type: Subunit vaccine
  • Status: Research
  • F1-ATPase gene engineering:
    • Type: Recombinant protein preparation
    • Detailed Gene Information: Click Here.
  • Adjuvant: cationic liposomal vaccine adjuvant DDA:TDB
  • Immunization Route: Intraperitoneal injection (i.p.)
  • Vaccine Ontology ID: VO_0011539
  • Type: Subunit vaccine
  • Status: Research
  • ORFF gene engineering:
    • Type: Recombinant protein preparation
    • Detailed Gene Information: Click Here.
  • Adjuvant: IL-12 vacince adjuvant
    • VO ID: VO_0001147
    • Description: An expression plasmid encoding both p35 and p40 subunits of IL-12 was used as an adjuvant (Tewary et al., 2006).
  • Immunization Route: Intramuscular injection (i.m.)
  • Vaccine Ontology ID: VO_0004241
  • Type: Subunit vaccine
  • Status: Research
  • Antigen: Recombinant Leishmania donovani gamma-glutamyl cysteine synthetase protein (LdγGCS) (Henriquez et al., 2010).
  • Adjuvant: non-ionic surfactant vesicles
  • Immunization Route: Intravenous injection (i.v.)
  • Vaccine Ontology ID: VO_0003005
  • Type: Live, attenuated vaccine
  • Status: Research
  • Host Species as Laboratory Animal Model: Mouse, hamster
  • cen1 gene engineering:
  • Immunization Route: Intravenous injection (i.v.)
  • Vaccine Ontology ID: VO_0004180
  • Type: Subunit vaccine
  • Status: Research
  • A2 gene engineering:
    • Type: Recombinant protein preparation
    • Detailed Gene Information: Click Here.
  • Vector: Leishmania tarentolae, a non-pathogenic member of the genus Leishmania (Mizbani et al., 2009).
  • Immunization Route: Intraperitoneal injection (i.p.)
  • Vaccine Ontology ID: VO_0004672
  • Type: Recombinant vector vaccine
  • Status: Research
  • Host Species for Licensed Use: Baboon
  • KMP-11 gene engineering:
    • Type: Recombinant vector construction
    • Description: The sequence encoding cholera toxin B subunit signal peptide was followed by SpeI/BglII sites for in frame directional cloning of ORF of interest fused with downstream sequences coding for a hemagglutinin epitope (HA)-tag and the transporter domain of AIDA (Schroeder et al., 2011)
    • Detailed Gene Information: Click Here.
  • Preparation: Five chosen antigens were differentially expressed on the surface or in the cytosol of Salmonella typhimurium SL3261. A two-step procedure was developed to select optimal Salmonella vaccine strains for each antigen, based on bacterial fitness and antigen expression levels (Schroeder et al., 2011).
  • Immunization Route: Intramuscular injection (i.m.)
Host Response Host Response Host Response Host Response Host Response Host Response Host Response Host Response Host Response Host Response Host Response Host Response Host Response

Mouse Response

  • Host Strain: BALB/c
  • Vaccination Protocol: Mice were immunized by intraperitoneal injections of 2.5 µg purified proteins in PBS or incorporated in liposome in a total volume of 200 µl. Animals receiving PBS or empty liposomes served as controls. Mice were boosted two times at 2-week intervals (Bhowmick and Ali, 2009).
  • Challenge Protocol: Ten days after the final immunization the mice were challenged with 2.5×107 freshly transformed stationary-phase promastigotes in 200 µl PBS injected intravenously via the tail vein (Bhowmick and Ali, 2009).
  • Efficacy: Results demonstrated that liposomal LD51 (beta-tubulin) reduced parasite burden by 72%-75% (Bhowmick and Ali, 2009).

Mouse Response

  • Host Strain: BALB/c
  • Vaccination Protocol: BALB/c mice were either immunized with KMP-11 containing pCMV-LIC mammalian expression vector (pCMV-LIC KMP-11) or with blank-vector construct not harboring KMP-11 gene (pCMV-LIC). rmIL-12 (1 μg/injection) was used as an adjuvant and injected through s.c. route. 7 and 15 days before parasite challenge with LD or LM, 100 μg of endotoxin-free plasmid DNA construct (pCMV-LIC, and pCMV-LIC KMP-11) dissolved in saline and injected i.m. in the hind leg thigh muscle was used for immunization of BALB/c mice using 28-gauge needle (Bhaumik et al., 2009).
  • Immune Response: KMP-11 DNA immunization alone effectively caused a significant increase in frequency of both IFN-γ producing CD4+ T and CD8+ T cells in mice challenged with either LM or LD (Bhaumik et al., 2009).
  • Challenge Protocol: 6-weeks-old BALB/c mice were injected with 2 × 106 LD second-passage promastigotes suspended in saline through intracardiac route and 2 × 106 LM second-passage promastigotes through subcutaneous route in the hind footpad using a 28-gauge needle (Bhaumik et al., 2009).
  • Efficacy: KMP-11 DNA vaccination alone in an experimental BALB/c mice model showed significant potential in terms of resolution of splenic and hepatic parasite burden against virulent LD challenge. KMP-11 DNA immunization significantly protects against L. donovani infection (Bhaumik et al., 2009).

Mouse Response

  • Host Strain: BALB/c
  • Vaccination Protocol: Mice were immunized via intramuscular with 100 μg of VR1012-NH36 plasmid DNA in 100 μl of saline solution and boosted 2 weeks later by a second injection. Control groups included the empty VR1012 vector and saline solution (Aguilar-Be et al., 2005).
  • Challenge Protocol: At 2 weeks after immunization, animals were challenged by intravenous injection of 2 × 108 amastigotes of L. chagasi (MHOM/BR/72/BH46), another group of mice were challenged 2 weeks after the last immunization with 106 stationary-phase promastigotes of L. mexicana (MNYC/BZ/62/379) by s.c. injection in the hind footpad (Aguilar-Be et al., 2005).
  • Efficacy: Experimental infection of immunized BALB/c mice demonstrated that the VR1012-NH36 DNA vaccine derived from the nucleoside hydrolase gene (NH) of L. donovani induced an 88% reduction in L. chagasi parasite load and a 65% reduction in L. mexicana lesion size (Aguilar-Be et al., 2005).

Mouse Response

  • Host Strain: BALB/c
  • Vaccination Protocol: BALB/c mice were immunized by three intraperitoneal (i.p.) injections at 2-week intervals with graded doses (0.6 to 10 μg) or 2.5 μg of gp63 free in phosphate-buffered saline (PBS) or entrapped in liposomes (200 μl). Animals receiving only PBS or empty liposomes served as controls (Bhowmick et al., 2008).
  • Challenge Protocol: At 10 days or 12 weeks postimmunization, groups of mice were either sacrificed for immunological assays or challenged intravenously with 2.5 × 107 freshly transformed L. donovani promastigotes (Bhowmick et al., 2008).
  • Efficacy: gp63 used without adjuvant elicited partial protection but in association with liposomes exhibited marked resistance in both the livers and spleens of the mice challenged 10 days after the last vaccination (Bhowmick et al., 2008).

Mouse Response

  • Host Strain: BALB/c
  • Vaccination Protocol: Ten microgram of 78 kDa antigen along with different concentrations of adjuvants was used to immunize animals. Subcutaneous route was used for immunization of mice in all the groups. Twenty-five BALB/c mice were used for each immunization group and the control group (immunized with PBS only).The animals who received only PBS as vaccine candidate served as controls. Two booster doses with the same respective vaccine combination were given to all immunized groups at an interval of 2 weeks each (Nagill and Kaur, 2010).
  • Challenge Protocol: Two weeks after last booster dose, mice of control and immunized groups were challenged with 1 × 107 promastigotes (Nagill and Kaur, 2010).
  • Efficacy: Maximum protection was conferred by 78 kDa antigen + rIL-12 vaccine (with parasite load reduction of 71–94.8% on 30–90 p.c.d.) (Nagill and Kaur, 2010)

Mouse Response

  • Host Strain: BALB/c
  • Vaccination Protocol: In the first two vaccination experiments, BALB/c mice received s.c. immunization with either 1) 10 µg rHASPB1 with 1 µg murine rIL-12; 2) 10 µg rHASPB1 in saline; 3) 10 µg SLA plus 1 µg rmIL-12; 4) 1 µg rmIL-12; and 5) saline. Three weeks later, mice were boosted with the same schedule, but the IL-12 dose was reduced to 0.5 µg. After an additional 3 wk, a final boost was given omitting IL-12. In the third vaccination experiment, mice were immunized three times at 3-wk intervals with 10 µg rHASPB1 or OVA (Sigma) (Stäger et al., 2000).
  • Challenge Protocol: All mice were challenged 3 wk after the last boost with 2 x 107 amastigotes, given i.v. in the lateral tail vein (Stäger et al., 2000).
  • Efficacy: rHASPB1 provided significant protection against challenge with L. donovani (Stäger et al., 2000).

Mouse Response

  • Host Strain: BALB/c
  • Vaccination Protocol: Mice were immunized by intraperitoneal injections of 2.5 µg purified proteins in PBS or incorporated in liposome in a total volume of 200 µl. Animals receiving PBS or empty liposomes served as controls. Mice were boosted two times at 2-week intervals (Bhowmick and Ali, 2009).
  • Challenge Protocol: Ten days after the final immunization rest of the mice were challenged with 2.5×107 freshly transformed stationary-phase promastigotes in 200 µl PBS injected intravenously via the tail vein (Bhowmick and Ali, 2009).
  • Efficacy: Mice immunized with liposomal LD72 (Hsp70) had a reduced parasite burden of 65%-67% (Bhowmick and Ali, 2009).

Mouse Response

  • Host Strain: BALB/c
  • Vaccination Protocol: Mice were immunized by intraperitoneal injections of 2.5 µg purified proteins in PBS or incorporated in liposome in a total volume of 200 µl. Animals receiving PBS or empty liposomes served as controls. Mice were boosted two times at 2-week intervals (Bhowmick and Ali, 2009).
  • Challenge Protocol: Ten days after the final immunization the mice were challenged with 2.5×107 freshly transformed stationary-phase promastigotes in 200 µl PBS injected intravenously via the tail vein (Bhowmick and Ali, 2009).
  • Efficacy: Liposomal LD31 (ATP synthase alpha chain) reduced parasite burden by 74%-77% (Bhowmick and Ali, 2009).

Mouse Response

  • Host Strain: BALB/c
  • Vaccination Protocol: Injections were given at midpoint of left thigh muscle. For the vaccination studies, cell proliferation, cytokine production and antibody response BALB/c mice were immunized intramuscularly with either alum alone diluted in phosphate buffered saline (PBS) final volume 100 or 50 μg of rORFF adsorbed on alum or 100 μg of IL-12 plasmid DNA diluted in PBS or 50 μg of rORFF adsorbed on alum in combination with IL-12 DNA. Three weeks later mice were immunized with the same schedule (Tewary et al., 2006).
  • Challenge Protocol: 1 × 108 stationary phase promastigotes of L. donovani were injected intravenously via the tail vein in 100 μl of PBS per mouse (Tewary et al., 2006).
  • Efficacy: An expression plasmid encoding both p35 and p40 subunits of IL-12 when co-administered with a recombinant open-reading frame (rORFF) gene from the LD1 locus of Leishmania donovani induces significant protection with around 82% protection in both liver and spleen of BALB/c mice when challenged with L. donovani (Tewary et al., 2006).

Mouse Response

  • Host Strain: BALB/c
  • Vaccination Protocol: The day of infection was day 0 so that vaccination occurred pre-infection on day −28 and day −14. Animals (n  =  5/treatment) were immunized with either LPS (10 ng/ml equivalent to 5 EU/ml, 1 ng/dose), LdγGCS (2 or 50 µg, used as prepared or processed to remove endotoxin), or LdγGCS incorporated into NIV (50 µg) on days −28 and −14 (Henriquez et al., 2010).
  • Challenge Protocol: On day 0 immunized mice and a control group (n  =  4–10/treatment) were infected by intravenous injection (tail vein, no anaesthetic) with 1–2 × 107 L. donovani strain 200016 amastigotes harvested from the spleen of an infected hamster (Henriquez et al., 2010).
  • Efficacy: Incorporating LdγGCS into a NIV formulation was more effective than immunization with LdγGCS alone based on its ability to induce specific antibody pre- and post-infection. However, the vesicular formulation gave a similar level of protection as immunization with LdγGCS alone (Henriquez et al., 2010).

Mouse Response

  • Persistence: A cen1 mutant is attenuated in mice (Selvapandiyan et al., 2009).
  • Efficacy: A cen1 mutant induces significant protection in mice from challenge with wild type L. donovani (Selvapandiyan et al., 2009).
  • Host Ifng (Interferon gamma) response
    • Description: The results thus indicate an increased IFN-γ secretion coinciding with reduced IL-10 production among the immunized mice. In the restimulated CD4+ T cells from the spleen, the IFN-γ/IL-10 ratio was significantly higher in the immunized mice both at the time of challenge (5 weeks after immunization) and after challenge (5 weeks after immunization plus 10 weeks after challenge) compared with either naive or naive-challenged controls. We also observed an absolute requirement for IFN-γ in LdCen1−/−-induced immunity. IFN-γ knockout mice immunized with LdCen1−/− for 5 wk followed by challenge were not protected (Selvapandiyan et al., 2009).
    • Detailed Gene Information: Click Here.
  • Host Ighv1-9 response
    • Description: Sera from BALB/c mice taken 10 wk post challenge after 5, 12, or 16 immunization weeks were measured for Leishmania-specific IgG2a responses. Results indicated a significantly higher level of IgG2a populations in the immune-challenged groups compared with the naive challenged groups (Selvapandiyan et al., 2009).
    • Detailed Gene Information: Click Here.
  • Host Il2 response
    • Description: The number of T cells producing IL-2 increased significantly as compared to naive mice 5 weeks after immunization in CD4+ and CD8+ cells as well as 5 weeks after immunization plus 10 weeks after challenge in both CD4+ and CD8+ cells (Selvapandiyan et al., 2009).
    • Detailed Gene Information: Click Here.
  • Host TNF-alpha response
    • Description: The number of T cells producing TNF-alpha increased significantly as compared to naive mice 5 weeks after immunization in CD8+ cells as well as 5 weeks after immunization plus 10 weeks after challenge in both CD4+ and CD8+ cells (Selvapandiyan et al., 2009).
    • Detailed Gene Information: Click Here.

Mouse Response

  • Host Strain: BALB/c
  • Vaccination Protocol: In the case of i.p. immunization, total number of 5 × 106 stationary-phase promastigotes were used. Mice were immunized with L. tarentolae expressing the GFP only as a control and another group were immunized with recombinant L. tarentolae-A2 (Mizbani et al., 2009).
  • Challenge Protocol: Six weeks after immunization, animals were challenged with 107 virulent stationary-phase L. infantum promastigotes through the lateral tail vein (Mizbani et al., 2009).
  • Efficacy: Study results show that a single intraperitoneal administration of the A2-recombinant L. tarentolae strain expressing the Leishmania donovani A2 antigen protects BALB/c mice against L. infantum challenge and that protective immunity is associated with high levels of IFN-gamma production prior and after challenge (Mizbani et al., 2009).

Mouse Response

  • Vaccination Protocol: Mice were vaccinated with a single dose of Salmonella vaccine strains, the carrier control SL3261 or treated with PBS (Schroeder et al., 2011).
  • Vaccine Immune Response Type: VO_0003057
  • Challenge Protocol: Mice were subsequently challenged with 2×106 late-stationary phase L. major promastigotes into the left hind footpad (Schroeder et al., 2011).
  • Efficacy: The vaccine strains of Salmonella expressing the novel Leishmania antigens LinJ08.1190 and LinJ23.0410 significantly reduced visceralisation of L. major and enhanced systemic resistance against L. donovani in susceptible BALB/c mice. The results show that Salmonella are valid vaccine carriers for inducing resistance against visceral leishmaniasis but that their use may not be suitable for all antigens (Schroeder et al., 2011).

Hamster Response

References References References References References References References References References References References References References
Bhowmick and Ali, 2009: Bhowmick S, Ali N. Identification of novel Leishmania donovani antigens that help define correlates of vaccine-mediated protection in visceral leishmaniasis. PloS one. 2009; 4(6); e5820. [PubMed: 19503834].
Bhaumik et al., 2009: Bhaumik S, Basu R, Sen S, Naskar K, Roy S. KMP-11 DNA immunization significantly protects against L. donovani infection but requires exogenous IL-12 as an adjuvant for comparable protection against L. major. Vaccine. 2009; 27(9); 1306-1316. [PubMed: 19162111].
Aguilar-Be et al., 2005: Aguilar-Be I, da Silva Zardo R, Paraguai de Souza E, Borja-Cabrera GP, Rosado-Vallado M, Mut-Martin M, García-Miss Mdel R, Palatnik de Sousa CB, Dumonteil E. Cross-protective efficacy of a prophylactic Leishmania donovani DNA vaccine against visceral and cutaneous murine leishmaniasis. Infection and immunity. 2005; 73(2); 812-819. [PubMed: 15664920].
Bhowmick et al., 2008: Bhowmick S, Ravindran R, Ali N. gp63 in stable cationic liposomes confers sustained vaccine immunity to susceptible BALB/c mice infected with Leishmania donovani. Infection and immunity. 2008; 76(3); 1003-1015. [PubMed: 18195029].
Nagill and Kaur, 2010: Nagill R, Kaur S. Enhanced efficacy and immunogenicity of 78kDa antigen formulated in various adjuvants against murine visceral leishmaniasis. Vaccine. 2010; 28(23); 4002-4012. [PubMed: 20093205].
Stäger et al., 2000: Stäger S, Smith DF, Kaye PM. Immunization with a recombinant stage-regulated surface protein from Leishmania donovani induces protection against visceral leishmaniasis. Journal of immunology (Baltimore, Md. : 1950). 2000; 165(12); 7064-7071. [PubMed: 11120835].
Bhowmick and Ali, 2009: Bhowmick S, Ali N. Identification of novel Leishmania donovani antigens that help define correlates of vaccine-mediated protection in visceral leishmaniasis. PloS one. 2009; 4(6); e5820. [PubMed: 19503834].
Bhowmick and Ali, 2009: Bhowmick S, Ali N. Identification of novel Leishmania donovani antigens that help define correlates of vaccine-mediated protection in visceral leishmaniasis. PloS one. 2009; 4(6); e5820. [PubMed: 19503834].
Tewary et al., 2006: Tewary P, Saxena S, Madhubala R. Co-administration of IL-12 DNA with rORFF antigen confers long-term protective immunity against experimental visceral leishmaniaisis. Vaccine. 2006; 24(13); 2409-2416. [PubMed: 16413950].
Henriquez et al., 2010: Henriquez FL, Campbell SA, Roberts CW, Mullen AB, Burchmore R, Carter KC. Vaccination with recombinant Leishmania donovani gamma-glutamylcysteine synthetase fusion protein protects against L. donovani infection. The Journal of parasitology. 2010; 96(5); 929-936. [PubMed: 20950100].
Selvapandiyan et al., 2009: Selvapandiyan A, Dey R, Nylen S, Duncan R, Sacks D, Nakhasi HL. Intracellular replication-deficient Leishmania donovani induces long lasting protective immunity against visceral leishmaniasis. Journal of immunology (Baltimore, Md. : 1950). 2009; 183(3); 1813-1820. [PubMed: 19592661].
Mizbani et al., 2009: Mizbani A, Taheri T, Zahedifard F, Taslimi Y, Azizi H, Azadmanesh K, Papadopoulou B, Rafati S. Recombinant Leishmania tarentolae expressing the A2 virulence gene as a novel candidate vaccine against visceral leishmaniasis. Vaccine. 2009; 28(1); 53-62. [PubMed: 19818721].
Schroeder et al., 2011: Schroeder J, Brown N, Kaye P, Aebischer T. Single dose novel Salmonella vaccine enhances resistance against visceralizing L. major and L. donovani infection in susceptible BALB/c mice. PLoS neglected tropical diseases. 2011; 5(12); e1406. [PubMed: 22216363].