Intranasal Vaccination against Cutaneous Leishmaniasis with a Particulated Leishmanial Antigen or DNA Encoding LACK
Open Access
- 1 August 2004
- journal article
- research article
- Published by American Society for Microbiology in Infection and Immunity
- Vol. 72 (8), 4521-4527
- https://doi.org/10.1128/iai.72.8.4521-4527.2004
Abstract
We have previously demonstrated that oral delivery of a disease-promoting particulated antigen of Leishmania amazonensis (LaAg) partially protects mice against cutaneous leishmaniasis. In the present work, we sought to optimize a mucosal vaccine by using the intranasal route for delivery of different antigen preparations, including (i) LaAg, (ii) soluble recombinant p36/LACK leishmanial antigen (LACK), and (iii) plasmid DNA encoding LACK (LACK DNA). BALB/c mice that received two intranasal doses of 10 μg of LaAg and were challenged 1 week postvaccination with L. amazonensis developed delayed but effective control of lesion growth. A diminished parasite burden was accompanied by enhancement of both gamma interferon (IFN-γ) and interleukin-10 levels in the lesion-draining lymph nodes. The vaccine efficacy improved with time. At 4 months postvaccination, when a strong parasite-specific TH1-type response was present in vivo, the infection was controlled for at least 5 months after challenge. In contrast to the particulated LaAg, soluble LACK (10 μg/dose) had no effect. Interestingly, LACK DNA (30 μg/dose), but not empty DNA, promoted rapid and durable protective immunity. Parasite growth was effectively controlled, and at 5 months after challenge LACK-reactive cells in both the mucosal and lesion-draining lymph nodes produced high levels of IFN-γ. These results demonstrate for the first time the feasibility of using the intranasal route for long-lived memory vaccination against cutaneous leishmaniasis with adjuvant-free crude antigens or DNA.Keywords
This publication has 42 references indexed in Scilit:
- ImmunologyJournal of Biomedical Science, 2004
- Single Intranasal MucosalMycobacterium bovisBCG Vaccination Confers Improved Protection Compared to Subcutaneous Vaccination against Pulmonary TuberculosisInfection and Immunity, 2004
- ImmunologyJournal of Biomedical Science, 2004
- The role of CD4+CD25+ regulatory T cells in Leishmania infectionExpert Opinion on Biological Therapy, 2003
- Early Enhanced Th1 Response afterLeishmania amazonensisInfection of C57BL/6 Interleukin-10-Deficient Mice Does Not Lead to Resolution of InfectionInfection and Immunity, 2002
- Pretreatment of Leishmania Homologue of Receptors for Activated C Kinase (LACK) Promotes Disease Progression Caused by Leishmania amazonensis.Experimental Animals, 2002
- Mucosal immunity and tolerance: relevance to vaccine developmentImmunological Reviews, 1999
- Phase 1 Study of an Inactivated Vaccine against American Tegumentary Leishmaniasis in Normal Volunteers in BrazilMemórias do Instituto Oswaldo Cruz, 1998
- The expanding universe of T-cell subsets: Th1, Th2 and moreImmunology Today, 1996
- The Regulation of Immunity to Leishmania MajorAnnual Review of Immunology, 1995