Vaccination with LetiFend® reduces circulating immune complexes in dogs experimentally infected with L. infantum
•The severity of canine leishmaniosis is associated to the presence of CIC.•The active substance consists on a chimeric protein composed by active epitopes.•LetiFend® reduced the levels of CIC in experimentally infected dogs.•Vaccinated dogs showed an increase of the proteins of the complement and t...
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| Veröffentlicht in: | Vaccine 2020-01, Vol.38 (4), p.890-896 |
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| creator | Cacheiro-Llaguno, Cristina Parody, Nuria Renshaw-Calderón, Ana Osuna, Cristina Alonso, Carlos Carnés, Jerónimo |
| description | •The severity of canine leishmaniosis is associated to the presence of CIC.•The active substance consists on a chimeric protein composed by active epitopes.•LetiFend® reduced the levels of CIC in experimentally infected dogs.•Vaccinated dogs showed an increase of the proteins of the complement and the serpin family.
Domestic dogs constitute the main reservoir of Leishmania infantum and play a key role in transmission to humans. The main tool for controlling infection spread is a safe and effective vaccine, as successful immunization of dogs could significantly reduce the incidence of human visceral leishmaniosis (VL) and is the most cost-effective control strategy.
The factors that determine disease progression in canine leishmaniosis (CanL) remain poorly understood, though a previous study in naturally infected dogs has demonstrated a clear relationship between the presence of circulating immune complexes (CIC) in the blood and disease progression. Thus, the aim of this study was to compare CIC levels in serum samples from dogs vaccinated or unvaccinated with LetiFend®, a new vaccine containing recombinant Protein Q, and experimentally infected with L. infantum.
CIC were isolated from vaccinated or unvaccinated dogs after experimental infection with L. infantum and their levels measured by ELISA. Furthermore, reverse phase-liquid chromatography-mass spectrometry (RP-LC-MS/MS) analysis was used to investigate the protein composition of precipitated CIC.
At all the time points analyzed after infection, the amount of CIC was lower in the vaccinated group compared to the placebo group. Furthermore, there were differences in the protein composition of precipitated CIC between the vaccinated and unvaccinated groups.
In conclusion, administration of LetiFend® was able to reduce CIC elicited after experimental infection with L. infantum in a dog model in a process that may be related to complement system activation. |
| doi_str_mv | 10.1016/j.vaccine.2019.10.078 |
| format | Article |
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Domestic dogs constitute the main reservoir of Leishmania infantum and play a key role in transmission to humans. The main tool for controlling infection spread is a safe and effective vaccine, as successful immunization of dogs could significantly reduce the incidence of human visceral leishmaniosis (VL) and is the most cost-effective control strategy.
The factors that determine disease progression in canine leishmaniosis (CanL) remain poorly understood, though a previous study in naturally infected dogs has demonstrated a clear relationship between the presence of circulating immune complexes (CIC) in the blood and disease progression. Thus, the aim of this study was to compare CIC levels in serum samples from dogs vaccinated or unvaccinated with LetiFend®, a new vaccine containing recombinant Protein Q, and experimentally infected with L. infantum.
CIC were isolated from vaccinated or unvaccinated dogs after experimental infection with L. infantum and their levels measured by ELISA. Furthermore, reverse phase-liquid chromatography-mass spectrometry (RP-LC-MS/MS) analysis was used to investigate the protein composition of precipitated CIC.
At all the time points analyzed after infection, the amount of CIC was lower in the vaccinated group compared to the placebo group. Furthermore, there were differences in the protein composition of precipitated CIC between the vaccinated and unvaccinated groups.
In conclusion, administration of LetiFend® was able to reduce CIC elicited after experimental infection with L. infantum in a dog model in a process that may be related to complement system activation.</description><identifier>ISSN: 0264-410X</identifier><identifier>EISSN: 1873-2518</identifier><identifier>DOI: 10.1016/j.vaccine.2019.10.078</identifier><identifier>PMID: 31706810</identifier><language>eng</language><publisher>Netherlands: Elsevier Ltd</publisher><subject>Animals ; Antigen-Antibody Complex - blood ; Antigen-antibody complexes ; Antigens ; Biomarkers ; Blood circulation ; Canine leishmaniosis ; Chromatography, Liquid ; Circulating immune complexes ; Complement activation ; Complement Activation - immunology ; Complement system ; Composition ; Disease control ; Disease Progression ; Dog Diseases - immunology ; Dog Diseases - microbiology ; Dog Diseases - prevention & control ; Dogs ; Domestic animals ; Experimental infection ; Female ; Immunization ; Infections ; Laboratories ; Leishmania infantum ; Leishmania infantum - immunology ; Leishmaniasis ; Leishmaniasis Vaccines - administration & dosage ; Leishmaniasis Vaccines - immunology ; Leishmaniasis, Visceral - immunology ; Leishmaniasis, Visceral - prevention & control ; Leishmaniasis, Visceral - veterinary ; LetiFend ; Levels ; Liquid chromatography ; Male ; Mass spectrometry ; Mass spectroscopy ; Parasites ; Penicillin ; Peptides ; Polyethylene glycol ; Protein composition ; Proteins ; Tandem Mass Spectrometry ; Time Factors ; Vaccination ; Vaccine ; Vaccines</subject><ispartof>Vaccine, 2020-01, Vol.38 (4), p.890-896</ispartof><rights>2019 Elsevier Ltd</rights><rights>Copyright © 2019 Elsevier Ltd. All rights reserved.</rights><rights>2019. Elsevier Ltd</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c393t-3c59860964738d162194acfe514a945c6e62dced1e0aa3a67de3acbb477391083</citedby><cites>FETCH-LOGICAL-c393t-3c59860964738d162194acfe514a945c6e62dced1e0aa3a67de3acbb477391083</cites><orcidid>0000-0003-4050-2577</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.proquest.com/docview/2336997773?pq-origsite=primo$$EHTML$$P50$$Gproquest$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995,64385,64387,64389,72469</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31706810$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Cacheiro-Llaguno, Cristina</creatorcontrib><creatorcontrib>Parody, Nuria</creatorcontrib><creatorcontrib>Renshaw-Calderón, Ana</creatorcontrib><creatorcontrib>Osuna, Cristina</creatorcontrib><creatorcontrib>Alonso, Carlos</creatorcontrib><creatorcontrib>Carnés, Jerónimo</creatorcontrib><title>Vaccination with LetiFend® reduces circulating immune complexes in dogs experimentally infected with L. infantum</title><title>Vaccine</title><addtitle>Vaccine</addtitle><description>•The severity of canine leishmaniosis is associated to the presence of CIC.•The active substance consists on a chimeric protein composed by active epitopes.•LetiFend® reduced the levels of CIC in experimentally infected dogs.•Vaccinated dogs showed an increase of the proteins of the complement and the serpin family.
Domestic dogs constitute the main reservoir of Leishmania infantum and play a key role in transmission to humans. The main tool for controlling infection spread is a safe and effective vaccine, as successful immunization of dogs could significantly reduce the incidence of human visceral leishmaniosis (VL) and is the most cost-effective control strategy.
The factors that determine disease progression in canine leishmaniosis (CanL) remain poorly understood, though a previous study in naturally infected dogs has demonstrated a clear relationship between the presence of circulating immune complexes (CIC) in the blood and disease progression. Thus, the aim of this study was to compare CIC levels in serum samples from dogs vaccinated or unvaccinated with LetiFend®, a new vaccine containing recombinant Protein Q, and experimentally infected with L. infantum.
CIC were isolated from vaccinated or unvaccinated dogs after experimental infection with L. infantum and their levels measured by ELISA. Furthermore, reverse phase-liquid chromatography-mass spectrometry (RP-LC-MS/MS) analysis was used to investigate the protein composition of precipitated CIC.
At all the time points analyzed after infection, the amount of CIC was lower in the vaccinated group compared to the placebo group. Furthermore, there were differences in the protein composition of precipitated CIC between the vaccinated and unvaccinated groups.
In conclusion, administration of LetiFend® was able to reduce CIC elicited after experimental infection with L. infantum in a dog model in a process that may be related to complement system activation.</description><subject>Animals</subject><subject>Antigen-Antibody Complex - blood</subject><subject>Antigen-antibody complexes</subject><subject>Antigens</subject><subject>Biomarkers</subject><subject>Blood circulation</subject><subject>Canine leishmaniosis</subject><subject>Chromatography, Liquid</subject><subject>Circulating immune complexes</subject><subject>Complement activation</subject><subject>Complement Activation - immunology</subject><subject>Complement system</subject><subject>Composition</subject><subject>Disease control</subject><subject>Disease Progression</subject><subject>Dog Diseases - immunology</subject><subject>Dog Diseases - microbiology</subject><subject>Dog Diseases - prevention & control</subject><subject>Dogs</subject><subject>Domestic animals</subject><subject>Experimental infection</subject><subject>Female</subject><subject>Immunization</subject><subject>Infections</subject><subject>Laboratories</subject><subject>Leishmania infantum</subject><subject>Leishmania infantum - immunology</subject><subject>Leishmaniasis</subject><subject>Leishmaniasis Vaccines - administration & dosage</subject><subject>Leishmaniasis Vaccines - immunology</subject><subject>Leishmaniasis, Visceral - immunology</subject><subject>Leishmaniasis, Visceral - prevention & control</subject><subject>Leishmaniasis, Visceral - veterinary</subject><subject>LetiFend</subject><subject>Levels</subject><subject>Liquid chromatography</subject><subject>Male</subject><subject>Mass spectrometry</subject><subject>Mass spectroscopy</subject><subject>Parasites</subject><subject>Penicillin</subject><subject>Peptides</subject><subject>Polyethylene glycol</subject><subject>Protein composition</subject><subject>Proteins</subject><subject>Tandem Mass Spectrometry</subject><subject>Time Factors</subject><subject>Vaccination</subject><subject>Vaccine</subject><subject>Vaccines</subject><issn>0264-410X</issn><issn>1873-2518</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNqFkUFu2zAQRYkiQe24PUILAdlkI5UjSpS4KoIgTgIY6CYJuiNocuzSkCiHlBz7Uj1ETlY6drrIJisCn28-Of8T8g1oBhT4j1W2UVpbh1lOQUQto1X9iYyhrlial1CfkDHNeZEWQH-PyFkIK0ppyUB8JiMGFeU10DF5enx1Ub3tXPJs-z_JDHs7RWde_iYezaAxJNp6PTSRccvEtu3gMNFdu25wGy-tS0y3DAlu1-hti65XTbOL8gJ1j-Zomu0F5fqh_UJOF6oJ-PV4TsjD9Pr-6jad_bq5u7qcpZoJ1qdMl6LmVPCiYrUBnoMolF5gCYUSRak58txoNIBUKaZ4ZZApPZ8XVcUE0JpNyMXBd-27pwFDL1sbNDaNctgNQeYMGC-piHlNyPk7dNUN3sXfRYpxIapoGqnyQGnfheBxIddxX-V3EqjcdyJX8tiJ3Heyl2Mnce770X2Yt2j-T72VEIGfBwBjHBuLXgZt0cXlrI8ZStPZD574ByEQoZk</recordid><startdate>20200122</startdate><enddate>20200122</enddate><creator>Cacheiro-Llaguno, Cristina</creator><creator>Parody, Nuria</creator><creator>Renshaw-Calderón, Ana</creator><creator>Osuna, Cristina</creator><creator>Alonso, Carlos</creator><creator>Carnés, Jerónimo</creator><general>Elsevier Ltd</general><general>Elsevier Limited</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QL</scope><scope>7RV</scope><scope>7T2</scope><scope>7T5</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88C</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9-</scope><scope>K9.</scope><scope>KB0</scope><scope>LK8</scope><scope>M0R</scope><scope>M0S</scope><scope>M0T</scope><scope>M1P</scope><scope>M2O</scope><scope>M7N</scope><scope>M7P</scope><scope>MBDVC</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0003-4050-2577</orcidid></search><sort><creationdate>20200122</creationdate><title>Vaccination with LetiFend® reduces circulating immune complexes in dogs experimentally infected with L. infantum</title><author>Cacheiro-Llaguno, Cristina ; Parody, Nuria ; Renshaw-Calderón, Ana ; Osuna, Cristina ; Alonso, Carlos ; Carnés, Jerónimo</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c393t-3c59860964738d162194acfe514a945c6e62dced1e0aa3a67de3acbb477391083</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Animals</topic><topic>Antigen-Antibody Complex - blood</topic><topic>Antigen-antibody complexes</topic><topic>Antigens</topic><topic>Biomarkers</topic><topic>Blood circulation</topic><topic>Canine leishmaniosis</topic><topic>Chromatography, Liquid</topic><topic>Circulating immune complexes</topic><topic>Complement activation</topic><topic>Complement Activation - immunology</topic><topic>Complement system</topic><topic>Composition</topic><topic>Disease control</topic><topic>Disease Progression</topic><topic>Dog Diseases - immunology</topic><topic>Dog Diseases - microbiology</topic><topic>Dog Diseases - prevention & control</topic><topic>Dogs</topic><topic>Domestic animals</topic><topic>Experimental infection</topic><topic>Female</topic><topic>Immunization</topic><topic>Infections</topic><topic>Laboratories</topic><topic>Leishmania infantum</topic><topic>Leishmania infantum - immunology</topic><topic>Leishmaniasis</topic><topic>Leishmaniasis Vaccines - administration & dosage</topic><topic>Leishmaniasis Vaccines - immunology</topic><topic>Leishmaniasis, Visceral - immunology</topic><topic>Leishmaniasis, Visceral - prevention & control</topic><topic>Leishmaniasis, Visceral - veterinary</topic><topic>LetiFend</topic><topic>Levels</topic><topic>Liquid chromatography</topic><topic>Male</topic><topic>Mass spectrometry</topic><topic>Mass spectroscopy</topic><topic>Parasites</topic><topic>Penicillin</topic><topic>Peptides</topic><topic>Polyethylene glycol</topic><topic>Protein composition</topic><topic>Proteins</topic><topic>Tandem Mass Spectrometry</topic><topic>Time Factors</topic><topic>Vaccination</topic><topic>Vaccine</topic><topic>Vaccines</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Cacheiro-Llaguno, Cristina</creatorcontrib><creatorcontrib>Parody, Nuria</creatorcontrib><creatorcontrib>Renshaw-Calderón, Ana</creatorcontrib><creatorcontrib>Osuna, Cristina</creatorcontrib><creatorcontrib>Alonso, Carlos</creatorcontrib><creatorcontrib>Carnés, Jerónimo</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Nursing & Allied Health Database</collection><collection>Health and Safety Science Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Healthcare Administration Database (Alumni)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>Consumer Health Database (Alumni Edition)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>ProQuest Biological Science Collection</collection><collection>Consumer Health Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Healthcare Administration Database</collection><collection>Medical Database</collection><collection>Research Library</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Research Library (Corporate)</collection><collection>Nursing & Allied Health Premium</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><jtitle>Vaccine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Cacheiro-Llaguno, Cristina</au><au>Parody, Nuria</au><au>Renshaw-Calderón, Ana</au><au>Osuna, Cristina</au><au>Alonso, Carlos</au><au>Carnés, Jerónimo</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Vaccination with LetiFend® reduces circulating immune complexes in dogs experimentally infected with L. infantum</atitle><jtitle>Vaccine</jtitle><addtitle>Vaccine</addtitle><date>2020-01-22</date><risdate>2020</risdate><volume>38</volume><issue>4</issue><spage>890</spage><epage>896</epage><pages>890-896</pages><issn>0264-410X</issn><eissn>1873-2518</eissn><abstract>•The severity of canine leishmaniosis is associated to the presence of CIC.•The active substance consists on a chimeric protein composed by active epitopes.•LetiFend® reduced the levels of CIC in experimentally infected dogs.•Vaccinated dogs showed an increase of the proteins of the complement and the serpin family.
Domestic dogs constitute the main reservoir of Leishmania infantum and play a key role in transmission to humans. The main tool for controlling infection spread is a safe and effective vaccine, as successful immunization of dogs could significantly reduce the incidence of human visceral leishmaniosis (VL) and is the most cost-effective control strategy.
The factors that determine disease progression in canine leishmaniosis (CanL) remain poorly understood, though a previous study in naturally infected dogs has demonstrated a clear relationship between the presence of circulating immune complexes (CIC) in the blood and disease progression. Thus, the aim of this study was to compare CIC levels in serum samples from dogs vaccinated or unvaccinated with LetiFend®, a new vaccine containing recombinant Protein Q, and experimentally infected with L. infantum.
CIC were isolated from vaccinated or unvaccinated dogs after experimental infection with L. infantum and their levels measured by ELISA. Furthermore, reverse phase-liquid chromatography-mass spectrometry (RP-LC-MS/MS) analysis was used to investigate the protein composition of precipitated CIC.
At all the time points analyzed after infection, the amount of CIC was lower in the vaccinated group compared to the placebo group. Furthermore, there were differences in the protein composition of precipitated CIC between the vaccinated and unvaccinated groups.
In conclusion, administration of LetiFend® was able to reduce CIC elicited after experimental infection with L. infantum in a dog model in a process that may be related to complement system activation.</abstract><cop>Netherlands</cop><pub>Elsevier Ltd</pub><pmid>31706810</pmid><doi>10.1016/j.vaccine.2019.10.078</doi><tpages>7</tpages><orcidid>https://orcid.org/0000-0003-4050-2577</orcidid></addata></record> |
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| subjects | Animals Antigen-Antibody Complex - blood Antigen-antibody complexes Antigens Biomarkers Blood circulation Canine leishmaniosis Chromatography, Liquid Circulating immune complexes Complement activation Complement Activation - immunology Complement system Composition Disease control Disease Progression Dog Diseases - immunology Dog Diseases - microbiology Dog Diseases - prevention & control Dogs Domestic animals Experimental infection Female Immunization Infections Laboratories Leishmania infantum Leishmania infantum - immunology Leishmaniasis Leishmaniasis Vaccines - administration & dosage Leishmaniasis Vaccines - immunology Leishmaniasis, Visceral - immunology Leishmaniasis, Visceral - prevention & control Leishmaniasis, Visceral - veterinary LetiFend Levels Liquid chromatography Male Mass spectrometry Mass spectroscopy Parasites Penicillin Peptides Polyethylene glycol Protein composition Proteins Tandem Mass Spectrometry Time Factors Vaccination Vaccine Vaccines |
| title | Vaccination with LetiFend® reduces circulating immune complexes in dogs experimentally infected with L. infantum |
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