Potency, Efficacy and Durability of DNA/DNA, DNA/ Protein and Protein/Protein Based Vaccination Using gp63 Against Leishmania donovani in BALB/c Mice
IR@IICB: CSIR-Indian Institute of Chemical Biology, Kolkata
View Archive Info| Field | Value | |
| Title |
Potency, Efficacy and Durability of DNA/DNA, DNA/
Protein and Protein/Protein Based Vaccination Using
gp63 Against Leishmania donovani in BALB/c Mice
|
|
| Creator |
Mazumder, Saumyabrata
Maji, Mithun Das, Amrita Ali, Nahid |
|
| Subject |
Infectious Diseases and Immunology
|
|
| Description |
Background:Visceral leishmaniasis (VL) caused by an intracellular protozoan parasite Leishmania, is fatal in the absence of
treatment. At present there are no effective vaccines against any form of leishmaniasis. Here, we evaluate the potency,
efficacy and durability of DNA/DNA, DNA-prime/Protein-boost, and Protein/Protein based vaccination against VL in a
susceptible murine model.
Methods and Findings:To compare the potency, efficacy, and durability of DNA, protein and heterologous prime-boost
(HPB) vaccination against Leishmania donovani, major surface glycoprotein gp63 was cloned into mammalian expression
vector pcDNA3.1 for DNA based vaccines. We demonstrated that gp63 DNA based vaccination induced immune responses
and conferred protection against challenge infection. However, vaccination with HPB approach showed comparatively
enhanced cellular and humoral responses than other regimens and elicited early mixed Th1/Th2 responses before infection.
Moreover, challenge with parasites induced polarized Th1 responses with enhanced IFN-c, IL-12, nitric oxide, IgG2a/IgG1
ratio and reduced IL-4 and IL-10 responses compared to other vaccination strategies. Although, vaccination with gp63 DNA
either alone or mixed with CpG- ODN or heterologously prime-boosting with CpG- ODN showed comparable levels of
protection at short-term protection study, DNA-prime/Protein-boost in presence of CpG significantly reduced hepatic and
splenic parasite load by 107 fold and 1010 fold respectively, in long-term study. The extent of protection, obtained in this
study has till now not been achieved in long-term protection through HPB approach in susceptible BALB/c model against
VL. Interestingly, the HPB regimen also showed marked reduction in the footpad swelling of BALB/c mice against
Leishmania major infection.
Conclusion/Significance: HPB approach based on gp63 in association with CpG, resulted in robust cellular and humoral
responses correlating with durable protection against L. donovani challenge till twelve weeks post-vaccination. These results
emphasize the potential of DNA-prime/Protein-boost vaccination over DNA/DNA and Protein/Protein based vaccination in
maintaining long-term immunity against intracellular pathogen like Leishmania.
|
|
| Date |
2011
|
|
| Type |
Article
PeerReviewed |
|
| Format |
application/pdf
|
|
| Identifier |
http://www.eprints.iicb.res.in/85/1/PLOS_ONE%2C6(2)%2C2011[88].pdf
Mazumder, Saumyabrata and Maji, Mithun and Das, Amrita and Ali, Nahid (2011) Potency, Efficacy and Durability of DNA/DNA, DNA/ Protein and Protein/Protein Based Vaccination Using gp63 Against Leishmania donovani in BALB/c Mice. PLoS ONE, 6 (2). |
|
| Relation |
http://dx.doi.org/10.1371/journal.pone.0014644
http://www.eprints.iicb.res.in/85/ |
|