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Infect. Immun. doi:10.1128/IAI.00611-07
Copyright (c) 2008, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Gp63 in Stable Cationic Liposomes Confers Sustained Vaccine Immunity to Susceptible BALB/c Mice Infected with Leishmania donovani

Indian Institute of Chemical Biology, Infectious Diseases and Immunology Division, Kolkata 700032, India

^* To whom correspondence should be addressed. Email: nali{at}iicb.res.in.

	Abstract

Visceral leishmaniasis is deadly if not treated and development of a vaccine with long-term immunity remains a challenge. In this study, we showed that cationic distearoyl phosphatidylcholine (DSPC) liposomes, when used as vaccine adjuvant with the immunodominant 63 kDa glycoprotein (gp63) of Leishmania donovani promastigotes, induced significant protection against progressive visceral leishmaniasis in susceptible BALB/c mice. Gp63 used without adjuvant elicited partial protection but in association with liposomes exhibited marked resistance in both liver and spleen of the mice challenged 10 days after the last vaccination. The protective efficacy of liposomal gp63 vaccination was dose-dependent with 2.5 µg protein showing optimal protection. The immunity conferred by this vaccine formulation was durable as mice challenged 12 weeks after immunization were still protected, and the infection was controlled for at least 3 months postchallenge. Production of gamma interferon (IFN- ) and interleukin-4 (IL-4) by splenic T cells, and serum IgG1 and IgG2a following immunization, suggested induction of a mixed Th1/Th2 response following immunization. However, the control of disease progression and parasitic burden in mice vaccinated with gp63 in cationic DSPC liposome was associated with enhancement of antigen-specific IFN- and downregulation of IL-4 demonstrating a Th1 bias. Long-term immunity elicited by this vaccine corresponded with, in addition to antigen-specific Th1, CD8⁺ T cell responses. Our results demonstrated that stable cationic liposomes containing gp63 acted as a potent adjuvant for protein antigen to induce long-term protection against L. donovani that represents an alternative to DNA vaccination.

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