Document Detail


Evaluation of recombinant Leishmania polyprotein plus glucopyranosyl lipid A stable emulsion vaccines against sand fly-transmitted Leishmania major in C57BL/6 mice.
MedLine Citation:
PMID:  23045616     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Numerous experimental Leishmania vaccines have been developed to prevent the visceral and cutaneous forms of Leishmaniasis, which occur after exposure to the bite of an infected sand fly, yet only one is under evaluation in humans. KSAC and L110f, recombinant Leishmania polyproteins delivered in a stable emulsion (SE) with the TLR4 agonists monophosphoryl lipid A or glucopyranosyl lipid A (GLA) have shown protection in animal models. KSAC+GLA-SE protected against cutaneous disease following sand fly transmission of Leishmania major in susceptible BALB/c mice. Similar polyprotein adjuvant combinations are the vaccine candidates most likely to see clinical evaluation. We assessed immunity generated by KSAC or L110f vaccination with GLA-SE following challenge with L. major by needle or infected sand fly bite in resistant C57BL/6 mice. Polyprotein-vaccinated mice had a 60-fold increase in CD4(+)IFN-γ(+) T cell numbers versus control animals at 2 wk post-needle inoculation of L. major, and this correlated with a 100-fold reduction in parasite load. Immunity did not, however, reach levels observed in mice with a healed primary infection. Following challenge by infected sand fly bite, polyprotein-vaccinated animals had comparable parasite loads, greater numbers of neutrophils at the challenge site, and reduced CD4(+)IFN-γ(+)/IL-17(+) ratios versus nonvaccinated controls. In contrast, healed animals had significantly reduced parasite loads and higher CD4(+)IFN-γ(+)/IL-17(+) ratios. These observations demonstrate that vaccine-induced protection against needle challenge does not necessarily translate to protection following challenge by infected sand fly bite.
Authors:
Nathan C Peters; Sylvie Bertholet; Phillip G Lawyer; Melanie Charmoy; Audrey Romano; Flavia L Ribeiro-Gomes; Lisa W Stamper; David L Sacks
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Intramural     Date:  2012-10-08
Journal Detail:
Title:  Journal of immunology (Baltimore, Md. : 1950)     Volume:  189     ISSN:  1550-6606     ISO Abbreviation:  J. Immunol.     Publication Date:  2012 Nov 
Date Detail:
Created Date:  2012-11-05     Completed Date:  2013-01-15     Revised Date:  2013-12-04    
Medline Journal Info:
Nlm Unique ID:  2985117R     Medline TA:  J Immunol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  4832-41     Citation Subset:  AIM; IM    
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MeSH Terms
Descriptor/Qualifier:
Adjuvants, Immunologic / pharmacology*
Animals
CD4-Positive T-Lymphocytes / immunology
Disease Models, Animal
Emulsions
Interferon-gamma / immunology
Interleukin-17 / immunology
Leishmania major / genetics,  immunology*
Leishmaniasis Vaccines / genetics,  immunology,  pharmacology*
Leishmaniasis, Cutaneous / genetics,  immunology,  prevention & control*,  transmission
Lipid A / analogs & derivatives*,  pharmacology
Mice
Mice, Inbred BALB C
Protozoan Proteins / genetics,  immunology,  pharmacology*
Psychodidae*
Recombinant Proteins / genetics,  immunology,  pharmacology
Chemical
Reg. No./Substance:
0/Adjuvants, Immunologic; 0/Emulsions; 0/Interleukin-17; 0/Leishmaniasis Vaccines; 0/Lipid A; 0/Protozoan Proteins; 0/Recombinant Proteins; 82115-62-6/Interferon-gamma; MWC0ET1L2P/monophosphoryl lipid A
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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