Vaccination with Liposomal Leishmanial Antigens Adjuvanted with Monophosphoryl Lipid−Trehalose Dicorynomycolate (MPL-TDM)Confers Long-Term Protection against Visceral Leishmaniasis through a Human Administrable Route
IR@IICB: CSIR-Indian Institute of Chemical Biology, Kolkata
View Archive Info| Field | Value | |
| Title |
Vaccination with Liposomal Leishmanial Antigens Adjuvanted with Monophosphoryl Lipid−Trehalose Dicorynomycolate (MPL-TDM)Confers Long-Term Protection against Visceral Leishmaniasis through a Human Administrable Route
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| Creator |
Ravindran, Rajesh
Maji, Mithun Ali, Nahid |
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| Subject |
Infectious Diseases and Immunology
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| Description |
The development of a long-term protective subunit vaccine
against visceral leishmaniasis depends on antigens and adjuvants that can
induce an appropriate immune response. The immunization of leishmanial
antigens alone shows limited efficacy in the absence of an appropriate
adjuvant. Earlier we demonstrated sustained protection against Leishmania
donovani with leishmanial antigens entrapped in cationic liposomes through
an intraperitoneal route. However, this route is not applicable for human
administration. Herein, we therefore evaluated the immune response and
protection induced by liposomal soluble leishmanial antigen (SLA)
formulated with monophosphoryl lipid−trehalose dicorynomycolate
(MPL-TDM) through a subcutaneous route. Subcutaneous immunization
of BALB/c mice with SLA entrapped in liposomes or with MPL-TDM
elicited partial protection against experimental visceral leishmaniasis. In
contrast, liposomal SLA adjuvanted with MPL-TDM induced significantly
higher levels of protection in liver and spleen in BALB/c mice challenged
10 days post-vaccination. Protection conferred by this formulation was
sustained up to 12 weeks of immunization, and infection was controlled for
at least 4 months of the challenge, similar to liposomal SLA immunization administered intraperitoneally. An analysis of cellular
immune responses of liposomal SLA + MPL-TDM immunized mice demonstrated the induction of IFN-γ and IgG2a antibody
production not only 10 days or 12 weeks post-vaccination but also 4 months after the challenge infection and a down regulation
of IL-4 production after infection. Moreover, long-term immunity elicited by this formulation was associated with IFN-γ
production also by CD8+ T cells. Taken together, our results suggest that liposomal SLA + MPL-TDM represent a good vaccine
formulation for the induction of durable protection against L. donovani through a human administrable route.
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| Date |
2012
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| Type |
Article
PeerReviewed |
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| Format |
application/pdf
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| Identifier |
http://www.eprints.iicb.res.in/1566/1/MOLECULAR_PHARMACEUTICS___9_(_1)_59%2D70;2012[93].pdf
Ravindran, Rajesh and Maji, Mithun and Ali, Nahid (2012) Vaccination with Liposomal Leishmanial Antigens Adjuvanted with Monophosphoryl Lipid−Trehalose Dicorynomycolate (MPL-TDM)Confers Long-Term Protection against Visceral Leishmaniasis through a Human Administrable Route. Molecular Pharmaceutics, 9 (1). pp. 59-70. |
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| Relation |
http://dx.doi.org/10.1021/mp2002494
http://www.eprints.iicb.res.in/1566/ |
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