KSAC, a defined Leishmania antigen, plus adjuvant protects against the virulence of L. major transmitted by its natural vector Phlebotomus duboscqi.
Recombinant KSAC and L110f are promising Leishmania vaccine candidates. Both antigens formulated in stable emulsions (SE) with the natural TLR4 agonist MPL® and L110f with the synthetic TLR4 agonist GLA in SE protected BALB/c mice against L. major infection following needle challenge. Considering th...
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doaj-66b7d8e5ac65409893efed54deb33b202020-11-24T20:47:02ZengPublic Library of Science (PLoS)PLoS Neglected Tropical Diseases1935-27271935-27352012-01-0164e161010.1371/journal.pntd.0001610KSAC, a defined Leishmania antigen, plus adjuvant protects against the virulence of L. major transmitted by its natural vector Phlebotomus duboscqi.Regis GomesClarissa TeixeiraFabiano OliveiraPhillip G LawyerDia-Eldin ElnaiemClaudio MenesesYasuyuki GotoAjay BhatiaRandall F HowardSteven G ReedJesus G ValenzuelaShaden KamhawiRecombinant KSAC and L110f are promising Leishmania vaccine candidates. Both antigens formulated in stable emulsions (SE) with the natural TLR4 agonist MPL® and L110f with the synthetic TLR4 agonist GLA in SE protected BALB/c mice against L. major infection following needle challenge. Considering the virulence of vector-transmitted Leishmania infections, we vaccinated BALB/c mice with either KSAC+GLA-SE or L110f+GLA-SE to assess protection against L. major transmitted via its vector Phlebotomus duboscqi.Mice receiving the KSAC or L110f vaccines were challenged by needle or L. major-infected sand flies. Weekly disease progression and terminal parasite loads were determined. Immunological responses to KSAC, L110f, or soluble Leishmania antigen (SLA) were assessed throughout vaccination, three and twelve weeks after immunization, and one week post-challenge.Following sand fly challenge, KSAC-vaccinated mice were protected while L110f-vaccinated animals showed partial protection. Protection correlated with the ability of SLA to induce IFN-γ-producing CD4(+)CD62L(low)CCR7(low) effector memory T cells pre- and post-sand fly challenge.This study demonstrates the protective efficacy of KSAC+GLA-SE against sand fly challenge; the importance of vector-transmitted challenge in evaluating vaccine candidates against Leishmania infection; and the necessity of a rapid potent Th1 response against Leishmania to attain true protection.http://europepmc.org/articles/PMC3317914?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Regis Gomes Clarissa Teixeira Fabiano Oliveira Phillip G Lawyer Dia-Eldin Elnaiem Claudio Meneses Yasuyuki Goto Ajay Bhatia Randall F Howard Steven G Reed Jesus G Valenzuela Shaden Kamhawi |
spellingShingle |
Regis Gomes Clarissa Teixeira Fabiano Oliveira Phillip G Lawyer Dia-Eldin Elnaiem Claudio Meneses Yasuyuki Goto Ajay Bhatia Randall F Howard Steven G Reed Jesus G Valenzuela Shaden Kamhawi KSAC, a defined Leishmania antigen, plus adjuvant protects against the virulence of L. major transmitted by its natural vector Phlebotomus duboscqi. PLoS Neglected Tropical Diseases |
author_facet |
Regis Gomes Clarissa Teixeira Fabiano Oliveira Phillip G Lawyer Dia-Eldin Elnaiem Claudio Meneses Yasuyuki Goto Ajay Bhatia Randall F Howard Steven G Reed Jesus G Valenzuela Shaden Kamhawi |
author_sort |
Regis Gomes |
title |
KSAC, a defined Leishmania antigen, plus adjuvant protects against the virulence of L. major transmitted by its natural vector Phlebotomus duboscqi. |
title_short |
KSAC, a defined Leishmania antigen, plus adjuvant protects against the virulence of L. major transmitted by its natural vector Phlebotomus duboscqi. |
title_full |
KSAC, a defined Leishmania antigen, plus adjuvant protects against the virulence of L. major transmitted by its natural vector Phlebotomus duboscqi. |
title_fullStr |
KSAC, a defined Leishmania antigen, plus adjuvant protects against the virulence of L. major transmitted by its natural vector Phlebotomus duboscqi. |
title_full_unstemmed |
KSAC, a defined Leishmania antigen, plus adjuvant protects against the virulence of L. major transmitted by its natural vector Phlebotomus duboscqi. |
title_sort |
ksac, a defined leishmania antigen, plus adjuvant protects against the virulence of l. major transmitted by its natural vector phlebotomus duboscqi. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS Neglected Tropical Diseases |
issn |
1935-2727 1935-2735 |
publishDate |
2012-01-01 |
description |
Recombinant KSAC and L110f are promising Leishmania vaccine candidates. Both antigens formulated in stable emulsions (SE) with the natural TLR4 agonist MPL® and L110f with the synthetic TLR4 agonist GLA in SE protected BALB/c mice against L. major infection following needle challenge. Considering the virulence of vector-transmitted Leishmania infections, we vaccinated BALB/c mice with either KSAC+GLA-SE or L110f+GLA-SE to assess protection against L. major transmitted via its vector Phlebotomus duboscqi.Mice receiving the KSAC or L110f vaccines were challenged by needle or L. major-infected sand flies. Weekly disease progression and terminal parasite loads were determined. Immunological responses to KSAC, L110f, or soluble Leishmania antigen (SLA) were assessed throughout vaccination, three and twelve weeks after immunization, and one week post-challenge.Following sand fly challenge, KSAC-vaccinated mice were protected while L110f-vaccinated animals showed partial protection. Protection correlated with the ability of SLA to induce IFN-γ-producing CD4(+)CD62L(low)CCR7(low) effector memory T cells pre- and post-sand fly challenge.This study demonstrates the protective efficacy of KSAC+GLA-SE against sand fly challenge; the importance of vector-transmitted challenge in evaluating vaccine candidates against Leishmania infection; and the necessity of a rapid potent Th1 response against Leishmania to attain true protection. |
url |
http://europepmc.org/articles/PMC3317914?pdf=render |
work_keys_str_mv |
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