A Sand Fly Salivary Protein Vaccine Shows Efficacy Against Vector-Transmitted Cutaneous Leishmaniasis in Nonhuman Primates
Currently, there are no commercially available human vaccines against leishmaniasis. In rodents, cellular immunity to salivary proteins of sand fly vectors is associated to protection against leishmaniasis, making them worthy targets for further exploration as vaccines. We demonstrate that nonhuman...
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| creator | Oliveira, Fabiano Rowton, Edgar Aslan, Hamide Gomes, Regis Castrovinci, Philip A Alvarenga, Patricia H Abdeladhim, Maha Teixeira, Clarissa Meneses, Claudio Kleeman, Lindsey T |
| description | Currently, there are no commercially available human vaccines against leishmaniasis. In rodents, cellular immunity to salivary proteins of sand fly vectors is associated to protection against leishmaniasis, making them worthy targets for further exploration as vaccines. We demonstrate that nonhuman primates (NHP) exposed to Phlebotomus duboscqi uninfected sand fly bites or immunized with salivary protein PdSP15 are protected against cutaneous leishmaniasis initiated by infected bites. Uninfected sand fly exposed and 7 of 10 PdSP15-immunized rhesus macaques displayed a significant reduction in disease and parasite burden compared to controls. Protection correlated to the early appearance of Leishmania-specific CD4 + IFN- micron + lymphocytes, suggesting that immunity to saliva or PdSP15 augments the host immune response to the parasites while maintaining minimal pathology. Notably, the 30% unprotected PdSP15-immunized NHP developed neither immunity to PdSP15 nor an accelerated Leishmania-specific immunity. Sera and peripheral blood mononuclear cells from individuals naturally exposed to P. duboscqi bites recognized PdSP15, demonstrating its immunogenicity in humans. PdSP15 sequence and structure show no homology to mammalian proteins, further demonstrating its potential as a component of a vaccine for human leishmaniasis.
Published in Science Translational Medicine, v7 n290 p1-12, 3 June 2015. |
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Published in Science Translational Medicine, v7 n290 p1-12, 3 June 2015.</description><language>eng</language><subject>ACCELERATED TESTING ; Anatomy and Physiology ; ANTIGEN ANTIBODY REACTIONS ; ASSAYING ; Biochemistry ; BITES AND STINGS ; BLOOD CELLS ; CULTURES(BIOLOGY) ; CYTOKINES ; DIPTERA ; DISEASE VECTORS ; ENZYMES ; EXPOSURE(PHYSIOLOGY) ; HISTOLOGY ; HOSTS(BIOLOGY) ; IMMUNOGENS ; INFECTED BITES ; INFECTIOUS DISEASES ; LEISHMANIASIS ; Medicine and Medical Research ; NHP(NONHUMAN PRIMATES) ; PARASITES ; PATHOPHYSIOLOGY ; PRIMATES ; PROTEINS ; RECEPTOR SITES(PHYSIOLOGY) ; RESPONSE(BIOLOGY) ; RODENTS ; SALIVA ; SAND FLIES ; SKIN TESTS ; STATISTICAL ANALYSIS ; TARGETS ; WINGED INSECTS</subject><creationdate>2015</creationdate><rights>Approved for public release; distribution is unlimited.</rights><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,778,883,27556,27557</link.rule.ids><linktorsrc>$$Uhttps://apps.dtic.mil/sti/citations/ADA622977$$EView_record_in_DTIC$$FView_record_in_$$GDTIC$$Hfree_for_read</linktorsrc></links><search><creatorcontrib>Oliveira, Fabiano</creatorcontrib><creatorcontrib>Rowton, Edgar</creatorcontrib><creatorcontrib>Aslan, Hamide</creatorcontrib><creatorcontrib>Gomes, Regis</creatorcontrib><creatorcontrib>Castrovinci, Philip A</creatorcontrib><creatorcontrib>Alvarenga, Patricia H</creatorcontrib><creatorcontrib>Abdeladhim, Maha</creatorcontrib><creatorcontrib>Teixeira, Clarissa</creatorcontrib><creatorcontrib>Meneses, Claudio</creatorcontrib><creatorcontrib>Kleeman, Lindsey T</creatorcontrib><creatorcontrib>WALTER REED ARMY INST OF RESEARCH SILVER SPRING MD DEPT OF ENTOMOLOGY</creatorcontrib><title>A Sand Fly Salivary Protein Vaccine Shows Efficacy Against Vector-Transmitted Cutaneous Leishmaniasis in Nonhuman Primates</title><description>Currently, there are no commercially available human vaccines against leishmaniasis. In rodents, cellular immunity to salivary proteins of sand fly vectors is associated to protection against leishmaniasis, making them worthy targets for further exploration as vaccines. We demonstrate that nonhuman primates (NHP) exposed to Phlebotomus duboscqi uninfected sand fly bites or immunized with salivary protein PdSP15 are protected against cutaneous leishmaniasis initiated by infected bites. Uninfected sand fly exposed and 7 of 10 PdSP15-immunized rhesus macaques displayed a significant reduction in disease and parasite burden compared to controls. Protection correlated to the early appearance of Leishmania-specific CD4 + IFN- micron + lymphocytes, suggesting that immunity to saliva or PdSP15 augments the host immune response to the parasites while maintaining minimal pathology. Notably, the 30% unprotected PdSP15-immunized NHP developed neither immunity to PdSP15 nor an accelerated Leishmania-specific immunity. Sera and peripheral blood mononuclear cells from individuals naturally exposed to P. duboscqi bites recognized PdSP15, demonstrating its immunogenicity in humans. PdSP15 sequence and structure show no homology to mammalian proteins, further demonstrating its potential as a component of a vaccine for human leishmaniasis.
Published in Science Translational Medicine, v7 n290 p1-12, 3 June 2015.</description><subject>ACCELERATED TESTING</subject><subject>Anatomy and Physiology</subject><subject>ANTIGEN ANTIBODY REACTIONS</subject><subject>ASSAYING</subject><subject>Biochemistry</subject><subject>BITES AND STINGS</subject><subject>BLOOD CELLS</subject><subject>CULTURES(BIOLOGY)</subject><subject>CYTOKINES</subject><subject>DIPTERA</subject><subject>DISEASE VECTORS</subject><subject>ENZYMES</subject><subject>EXPOSURE(PHYSIOLOGY)</subject><subject>HISTOLOGY</subject><subject>HOSTS(BIOLOGY)</subject><subject>IMMUNOGENS</subject><subject>INFECTED BITES</subject><subject>INFECTIOUS DISEASES</subject><subject>LEISHMANIASIS</subject><subject>Medicine and Medical Research</subject><subject>NHP(NONHUMAN PRIMATES)</subject><subject>PARASITES</subject><subject>PATHOPHYSIOLOGY</subject><subject>PRIMATES</subject><subject>PROTEINS</subject><subject>RECEPTOR SITES(PHYSIOLOGY)</subject><subject>RESPONSE(BIOLOGY)</subject><subject>RODENTS</subject><subject>SALIVA</subject><subject>SAND FLIES</subject><subject>SKIN TESTS</subject><subject>STATISTICAL ANALYSIS</subject><subject>TARGETS</subject><subject>WINGED INSECTS</subject><fulltext>true</fulltext><rsrctype>report</rsrctype><creationdate>2015</creationdate><recordtype>report</recordtype><sourceid>1RU</sourceid><recordid>eNqFjbEKwkAQRNNYiPoHFvsDaSIYLI-YYCEiRNKG5bIxC8kd3G6U-PVeYW81wzx4s04-Bmp0HVTjEsvILwwL3INXYgcNWsuOoB78W6Dse7ZoFzBPZCcKDVn1IX0EdDKxKnVQzIqO_CxwJZZhQscoLBBlN--GOQ7RzhMqyTZZ9TgK7X65SfZV-SguaadsW9H4rK05m2OWnfL88Ad_AQ_TQ7s</recordid><startdate>20150603</startdate><enddate>20150603</enddate><creator>Oliveira, Fabiano</creator><creator>Rowton, Edgar</creator><creator>Aslan, Hamide</creator><creator>Gomes, Regis</creator><creator>Castrovinci, Philip A</creator><creator>Alvarenga, Patricia H</creator><creator>Abdeladhim, Maha</creator><creator>Teixeira, Clarissa</creator><creator>Meneses, Claudio</creator><creator>Kleeman, Lindsey T</creator><scope>1RU</scope><scope>BHM</scope></search><sort><creationdate>20150603</creationdate><title>A Sand Fly Salivary Protein Vaccine Shows Efficacy Against Vector-Transmitted Cutaneous Leishmaniasis in Nonhuman Primates</title><author>Oliveira, Fabiano ; Rowton, Edgar ; Aslan, Hamide ; Gomes, Regis ; Castrovinci, Philip A ; Alvarenga, Patricia H ; Abdeladhim, Maha ; Teixeira, Clarissa ; Meneses, Claudio ; Kleeman, Lindsey T</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-dtic_stinet_ADA6229773</frbrgroupid><rsrctype>reports</rsrctype><prefilter>reports</prefilter><language>eng</language><creationdate>2015</creationdate><topic>ACCELERATED TESTING</topic><topic>Anatomy and Physiology</topic><topic>ANTIGEN ANTIBODY REACTIONS</topic><topic>ASSAYING</topic><topic>Biochemistry</topic><topic>BITES AND STINGS</topic><topic>BLOOD CELLS</topic><topic>CULTURES(BIOLOGY)</topic><topic>CYTOKINES</topic><topic>DIPTERA</topic><topic>DISEASE VECTORS</topic><topic>ENZYMES</topic><topic>EXPOSURE(PHYSIOLOGY)</topic><topic>HISTOLOGY</topic><topic>HOSTS(BIOLOGY)</topic><topic>IMMUNOGENS</topic><topic>INFECTED BITES</topic><topic>INFECTIOUS DISEASES</topic><topic>LEISHMANIASIS</topic><topic>Medicine and Medical Research</topic><topic>NHP(NONHUMAN PRIMATES)</topic><topic>PARASITES</topic><topic>PATHOPHYSIOLOGY</topic><topic>PRIMATES</topic><topic>PROTEINS</topic><topic>RECEPTOR SITES(PHYSIOLOGY)</topic><topic>RESPONSE(BIOLOGY)</topic><topic>RODENTS</topic><topic>SALIVA</topic><topic>SAND FLIES</topic><topic>SKIN TESTS</topic><topic>STATISTICAL ANALYSIS</topic><topic>TARGETS</topic><topic>WINGED INSECTS</topic><toplevel>online_resources</toplevel><creatorcontrib>Oliveira, Fabiano</creatorcontrib><creatorcontrib>Rowton, Edgar</creatorcontrib><creatorcontrib>Aslan, Hamide</creatorcontrib><creatorcontrib>Gomes, Regis</creatorcontrib><creatorcontrib>Castrovinci, Philip A</creatorcontrib><creatorcontrib>Alvarenga, Patricia H</creatorcontrib><creatorcontrib>Abdeladhim, Maha</creatorcontrib><creatorcontrib>Teixeira, Clarissa</creatorcontrib><creatorcontrib>Meneses, Claudio</creatorcontrib><creatorcontrib>Kleeman, Lindsey T</creatorcontrib><creatorcontrib>WALTER REED ARMY INST OF RESEARCH SILVER SPRING MD DEPT OF ENTOMOLOGY</creatorcontrib><collection>DTIC Technical Reports</collection><collection>DTIC STINET</collection></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext_linktorsrc</fulltext></delivery><addata><au>Oliveira, Fabiano</au><au>Rowton, Edgar</au><au>Aslan, Hamide</au><au>Gomes, Regis</au><au>Castrovinci, Philip A</au><au>Alvarenga, Patricia H</au><au>Abdeladhim, Maha</au><au>Teixeira, Clarissa</au><au>Meneses, Claudio</au><au>Kleeman, Lindsey T</au><aucorp>WALTER REED ARMY INST OF RESEARCH SILVER SPRING MD DEPT OF ENTOMOLOGY</aucorp><format>book</format><genre>unknown</genre><ristype>RPRT</ristype><btitle>A Sand Fly Salivary Protein Vaccine Shows Efficacy Against Vector-Transmitted Cutaneous Leishmaniasis in Nonhuman Primates</btitle><date>2015-06-03</date><risdate>2015</risdate><abstract>Currently, there are no commercially available human vaccines against leishmaniasis. In rodents, cellular immunity to salivary proteins of sand fly vectors is associated to protection against leishmaniasis, making them worthy targets for further exploration as vaccines. We demonstrate that nonhuman primates (NHP) exposed to Phlebotomus duboscqi uninfected sand fly bites or immunized with salivary protein PdSP15 are protected against cutaneous leishmaniasis initiated by infected bites. Uninfected sand fly exposed and 7 of 10 PdSP15-immunized rhesus macaques displayed a significant reduction in disease and parasite burden compared to controls. Protection correlated to the early appearance of Leishmania-specific CD4 + IFN- micron + lymphocytes, suggesting that immunity to saliva or PdSP15 augments the host immune response to the parasites while maintaining minimal pathology. Notably, the 30% unprotected PdSP15-immunized NHP developed neither immunity to PdSP15 nor an accelerated Leishmania-specific immunity. Sera and peripheral blood mononuclear cells from individuals naturally exposed to P. duboscqi bites recognized PdSP15, demonstrating its immunogenicity in humans. PdSP15 sequence and structure show no homology to mammalian proteins, further demonstrating its potential as a component of a vaccine for human leishmaniasis.
Published in Science Translational Medicine, v7 n290 p1-12, 3 June 2015.</abstract><oa>free_for_read</oa></addata></record> |
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| subjects | ACCELERATED TESTING Anatomy and Physiology ANTIGEN ANTIBODY REACTIONS ASSAYING Biochemistry BITES AND STINGS BLOOD CELLS CULTURES(BIOLOGY) CYTOKINES DIPTERA DISEASE VECTORS ENZYMES EXPOSURE(PHYSIOLOGY) HISTOLOGY HOSTS(BIOLOGY) IMMUNOGENS INFECTED BITES INFECTIOUS DISEASES LEISHMANIASIS Medicine and Medical Research NHP(NONHUMAN PRIMATES) PARASITES PATHOPHYSIOLOGY PRIMATES PROTEINS RECEPTOR SITES(PHYSIOLOGY) RESPONSE(BIOLOGY) RODENTS SALIVA SAND FLIES SKIN TESTS STATISTICAL ANALYSIS TARGETS WINGED INSECTS |
| title | A Sand Fly Salivary Protein Vaccine Shows Efficacy Against Vector-Transmitted Cutaneous Leishmaniasis in Nonhuman Primates |
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