CD4+ and CD8+ T-cell multi-epitope chimeric protein associated with an MPLA adjuvant induce protective efficacy and long-term immunological memory for the immunoprophylaxis of American Tegumentary Leishmaniasis
American Tegumentary Leishmaniasis (ATL) is a disease of high severity and incidence in Brazil, in addition to being a worldwide concern in public health. Leishmania amazonensis is one of the etiological agents of ATL, and the inefficiency of control measures, associated with the high toxicity of th...
Gespeichert in:
| Veröffentlicht in: | Vaccine 2024-08, Vol.42 (21), p.126178, Article 126178 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | |
|---|---|
| container_issue | 21 |
| container_start_page | 126178 |
| container_title | Vaccine |
| container_volume | 42 |
| creator | Moura, Dênia Monteiro de Carvalho, Ana Maria Ravena Severino Brito, Rory Cristiane Fortes de Roatt, Bruno Mendes Lage, Daniela Pagliara Martins, Vivian Tamietti Cruz, Luiza dos Reis Medeiros, Fernanda Alvarenga Cardoso Batista, Sarah Dutra Pinheiro, Guilherme Rafael Gomide da Costa Rocha, Manoel Otávio Coelho, Eduardo Antonio Ferraz Duarte, Mariana Costa Mendes, Tiago Antônio de Oliveira Menezes-Souza, Daniel |
| description | American Tegumentary Leishmaniasis (ATL) is a disease of high severity and incidence in Brazil, in addition to being a worldwide concern in public health. Leishmania amazonensis is one of the etiological agents of ATL, and the inefficiency of control measures, associated with the high toxicity of the treatment and the lack of effective immunoprophylactic strategies, makes the development of vaccines indispensable and imminent. In this light, the present study proposes to elaborate a chimeric protein (rChiP), based on the fusion of multiple epitopes of CD4+/CD8+ T cells, identified in the immunoproteome of the parasites L. amazonensis and L. braziliensis. The designed chimeric protein was tested in the L. amazonensis murine model of infection using the following formulations: 25 μg of the rChiP in saline (rChiP group) and 25 μg of the rChiP plus 25 μg of MPLA-PHAD® (rChiP+MPLA group). After completing immunization, CD4+ and CD8+ T cells, stimulated with SLa-Antigen or rChiP, showed an increased production of nitric oxide and intracytoplasmic pro-inflammatory cytokines, in addition to the generation of central and effector memory T cells. rChiP and rChiP+MPLA formulations were able to promote an effective protection against L. amazonensis infection determined by a reduction in the development of skin lesions and lower parasitic burden. Reduction in the development of skin lesions and lower parasitic burden in the vaccinated groups were associated with an increase of nitrite, CD4+/CD8+IFN-γ+TNF-α+ and CD4+/CD8+CD44highCD62Lhigh/low T cells, IgGTotal, IgG2a, and lower rates of IgG1 and CD4+/CD8+IL-10+. This data suggests that proposed formulations could be considered potential tools to prevent ATL.
[Display omitted]
•Rational strategy to develop antigens.•Integration between immunoproteomic and immunoinformatics analyses.•Chimeric protein shows high performance in ATL diagnosis. |
| doi_str_mv | 10.1016/j.vaccine.2024.126178 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_3154247965</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S0264410X24008417</els_id><sourcerecordid>3087698476</sourcerecordid><originalsourceid>FETCH-LOGICAL-c304t-466968e95f41e9d8d13e1a230a8c1b75af79efec55e999b4198e8ba7086365633</originalsourceid><addsrcrecordid>eNqFks-O0zAQxiMEYsvCI4AscVlplWIntmOfUNXln1QEhyJxs1xn0rqK7RI7hb4mT4S7KRy47MmH-X3zzYy_onhJ8Jxgwt_s50dtjPUwr3BF56TipBGPihkRTV1WjIjHxQxXnJaU4O9XxbMY9xhjVhP5tLiqJZa84WxW_F7e0VukfYuWd-IWrUsDfY_c2CdbwsGmcABkdtbBYA06DCGB9UjHGIzVCVr006ZdlqPPX1cLpNv9eNQ-Ievb0cDEm2SPgKDrrNHmdG_VB78tEwwOWedGH_qwzcVsCy4MJ9SFAaUdXIq5yWF36vUvG1Ho0OJ-lOy4hu3owCedFSuwcee0tzra-Lx40uk-wovLe118e_9uvfxYrr58-LRcrEpTY5pKyrnkAiTrKAHZipbUQHRVYy0M2TRMd42EDgxjIKXcUCIFiI1usOA1Z7yur4ubqW-e8McIMSln4_l82kMYo6oJoxVtJGcPo1g0XAra8Iy-_g_dh3HweZFMSVo3hLMmU2yizBBiHKBTh8G6fApFsDrnQ-3VJR_qnA815SPrXl26jxsH7T_V30Bk4O0EQL7c0cKgorHgDbR2yF-p2mAfsPgDwRjRbw</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>3094371657</pqid></control><display><type>article</type><title>CD4+ and CD8+ T-cell multi-epitope chimeric protein associated with an MPLA adjuvant induce protective efficacy and long-term immunological memory for the immunoprophylaxis of American Tegumentary Leishmaniasis</title><source>MEDLINE</source><source>ScienceDirect Journals (5 years ago - present)</source><source>ProQuest Central UK/Ireland</source><creator>Moura, Dênia Monteiro de ; Carvalho, Ana Maria Ravena Severino ; Brito, Rory Cristiane Fortes de ; Roatt, Bruno Mendes ; Lage, Daniela Pagliara ; Martins, Vivian Tamietti ; Cruz, Luiza dos Reis ; Medeiros, Fernanda Alvarenga Cardoso ; Batista, Sarah Dutra ; Pinheiro, Guilherme Rafael Gomide ; da Costa Rocha, Manoel Otávio ; Coelho, Eduardo Antonio Ferraz ; Duarte, Mariana Costa ; Mendes, Tiago Antônio de Oliveira ; Menezes-Souza, Daniel</creator><creatorcontrib>Moura, Dênia Monteiro de ; Carvalho, Ana Maria Ravena Severino ; Brito, Rory Cristiane Fortes de ; Roatt, Bruno Mendes ; Lage, Daniela Pagliara ; Martins, Vivian Tamietti ; Cruz, Luiza dos Reis ; Medeiros, Fernanda Alvarenga Cardoso ; Batista, Sarah Dutra ; Pinheiro, Guilherme Rafael Gomide ; da Costa Rocha, Manoel Otávio ; Coelho, Eduardo Antonio Ferraz ; Duarte, Mariana Costa ; Mendes, Tiago Antônio de Oliveira ; Menezes-Souza, Daniel</creatorcontrib><description>American Tegumentary Leishmaniasis (ATL) is a disease of high severity and incidence in Brazil, in addition to being a worldwide concern in public health. Leishmania amazonensis is one of the etiological agents of ATL, and the inefficiency of control measures, associated with the high toxicity of the treatment and the lack of effective immunoprophylactic strategies, makes the development of vaccines indispensable and imminent. In this light, the present study proposes to elaborate a chimeric protein (rChiP), based on the fusion of multiple epitopes of CD4+/CD8+ T cells, identified in the immunoproteome of the parasites L. amazonensis and L. braziliensis. The designed chimeric protein was tested in the L. amazonensis murine model of infection using the following formulations: 25 μg of the rChiP in saline (rChiP group) and 25 μg of the rChiP plus 25 μg of MPLA-PHAD® (rChiP+MPLA group). After completing immunization, CD4+ and CD8+ T cells, stimulated with SLa-Antigen or rChiP, showed an increased production of nitric oxide and intracytoplasmic pro-inflammatory cytokines, in addition to the generation of central and effector memory T cells. rChiP and rChiP+MPLA formulations were able to promote an effective protection against L. amazonensis infection determined by a reduction in the development of skin lesions and lower parasitic burden. Reduction in the development of skin lesions and lower parasitic burden in the vaccinated groups were associated with an increase of nitrite, CD4+/CD8+IFN-γ+TNF-α+ and CD4+/CD8+CD44highCD62Lhigh/low T cells, IgGTotal, IgG2a, and lower rates of IgG1 and CD4+/CD8+IL-10+. This data suggests that proposed formulations could be considered potential tools to prevent ATL.
[Display omitted]
•Rational strategy to develop antigens.•Integration between immunoproteomic and immunoinformatics analyses.•Chimeric protein shows high performance in ATL diagnosis.</description><identifier>ISSN: 0264-410X</identifier><identifier>ISSN: 1873-2518</identifier><identifier>EISSN: 1873-2518</identifier><identifier>DOI: 10.1016/j.vaccine.2024.126178</identifier><identifier>PMID: 39096765</identifier><language>eng</language><publisher>Netherlands: Elsevier Ltd</publisher><subject>Adjuvants ; Adjuvants, Immunologic - administration & dosage ; American Tegumentary Leishmaniasis ; Animal models ; Animals ; Antibodies, Protozoan - immunology ; Antigens ; Antigens, Protozoan - immunology ; Brazil ; CD4 antigen ; CD4-Positive T-Lymphocytes - immunology ; CD8 antigen ; CD8-positive T-lymphocytes ; CD8-Positive T-Lymphocytes - immunology ; Cell fusion ; Chimeric protein ; Chromatography ; cytokines ; Cytokines - immunology ; Cytokines - metabolism ; Disease control ; Disease Models, Animal ; Effectiveness ; Effector cells ; Epitopes ; Epitopes, T-Lymphocyte - immunology ; Etiology ; Female ; Fusion protein ; Immunization ; Immunoglobulin G ; Immunoinformatics ; Immunologic Memory ; Immunological memory ; Immunology ; Immunoprophylaxis ; Leishmania amazonensis ; Leishmania braziliensis - immunology ; leishmaniasis ; Leishmaniasis Vaccines - immunology ; Leishmaniasis, Cutaneous - immunology ; Leishmaniasis, Cutaneous - prevention & control ; Lesions ; Lipid A - analogs & derivatives ; Lipid A - immunology ; Lymphocytes ; Lymphocytes T ; memory ; Memory cells ; Mice ; Mice, Inbred BALB C ; Nitric oxide ; nitrites ; parasite load ; Parasites ; Parasitic diseases ; Proteins ; Protozoa ; Public health ; Reagents ; recombinant fusion proteins ; Recombinant Fusion Proteins - genetics ; Recombinant Fusion Proteins - immunology ; Skin diseases ; Skin lesions ; T-cell epitope mapping ; Tegumentary leishmaniasis ; Toxicity ; Tumor necrosis factor-α ; Vaccine ; Vaccines ; Vector-borne diseases ; γ-Interferon</subject><ispartof>Vaccine, 2024-08, Vol.42 (21), p.126178, Article 126178</ispartof><rights>2024 Elsevier Ltd</rights><rights>Copyright © 2024 Elsevier Ltd. All rights reserved.</rights><rights>2024. Elsevier Ltd</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c304t-466968e95f41e9d8d13e1a230a8c1b75af79efec55e999b4198e8ba7086365633</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.proquest.com/docview/3094371657?pq-origsite=primo$$EHTML$$P50$$Gproquest$$H</linktohtml><link.rule.ids>314,778,782,3539,27911,27912,45982,64370,64372,64374,72226</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/39096765$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Moura, Dênia Monteiro de</creatorcontrib><creatorcontrib>Carvalho, Ana Maria Ravena Severino</creatorcontrib><creatorcontrib>Brito, Rory Cristiane Fortes de</creatorcontrib><creatorcontrib>Roatt, Bruno Mendes</creatorcontrib><creatorcontrib>Lage, Daniela Pagliara</creatorcontrib><creatorcontrib>Martins, Vivian Tamietti</creatorcontrib><creatorcontrib>Cruz, Luiza dos Reis</creatorcontrib><creatorcontrib>Medeiros, Fernanda Alvarenga Cardoso</creatorcontrib><creatorcontrib>Batista, Sarah Dutra</creatorcontrib><creatorcontrib>Pinheiro, Guilherme Rafael Gomide</creatorcontrib><creatorcontrib>da Costa Rocha, Manoel Otávio</creatorcontrib><creatorcontrib>Coelho, Eduardo Antonio Ferraz</creatorcontrib><creatorcontrib>Duarte, Mariana Costa</creatorcontrib><creatorcontrib>Mendes, Tiago Antônio de Oliveira</creatorcontrib><creatorcontrib>Menezes-Souza, Daniel</creatorcontrib><title>CD4+ and CD8+ T-cell multi-epitope chimeric protein associated with an MPLA adjuvant induce protective efficacy and long-term immunological memory for the immunoprophylaxis of American Tegumentary Leishmaniasis</title><title>Vaccine</title><addtitle>Vaccine</addtitle><description>American Tegumentary Leishmaniasis (ATL) is a disease of high severity and incidence in Brazil, in addition to being a worldwide concern in public health. Leishmania amazonensis is one of the etiological agents of ATL, and the inefficiency of control measures, associated with the high toxicity of the treatment and the lack of effective immunoprophylactic strategies, makes the development of vaccines indispensable and imminent. In this light, the present study proposes to elaborate a chimeric protein (rChiP), based on the fusion of multiple epitopes of CD4+/CD8+ T cells, identified in the immunoproteome of the parasites L. amazonensis and L. braziliensis. The designed chimeric protein was tested in the L. amazonensis murine model of infection using the following formulations: 25 μg of the rChiP in saline (rChiP group) and 25 μg of the rChiP plus 25 μg of MPLA-PHAD® (rChiP+MPLA group). After completing immunization, CD4+ and CD8+ T cells, stimulated with SLa-Antigen or rChiP, showed an increased production of nitric oxide and intracytoplasmic pro-inflammatory cytokines, in addition to the generation of central and effector memory T cells. rChiP and rChiP+MPLA formulations were able to promote an effective protection against L. amazonensis infection determined by a reduction in the development of skin lesions and lower parasitic burden. Reduction in the development of skin lesions and lower parasitic burden in the vaccinated groups were associated with an increase of nitrite, CD4+/CD8+IFN-γ+TNF-α+ and CD4+/CD8+CD44highCD62Lhigh/low T cells, IgGTotal, IgG2a, and lower rates of IgG1 and CD4+/CD8+IL-10+. This data suggests that proposed formulations could be considered potential tools to prevent ATL.
[Display omitted]
•Rational strategy to develop antigens.•Integration between immunoproteomic and immunoinformatics analyses.•Chimeric protein shows high performance in ATL diagnosis.</description><subject>Adjuvants</subject><subject>Adjuvants, Immunologic - administration & dosage</subject><subject>American Tegumentary Leishmaniasis</subject><subject>Animal models</subject><subject>Animals</subject><subject>Antibodies, Protozoan - immunology</subject><subject>Antigens</subject><subject>Antigens, Protozoan - immunology</subject><subject>Brazil</subject><subject>CD4 antigen</subject><subject>CD4-Positive T-Lymphocytes - immunology</subject><subject>CD8 antigen</subject><subject>CD8-positive T-lymphocytes</subject><subject>CD8-Positive T-Lymphocytes - immunology</subject><subject>Cell fusion</subject><subject>Chimeric protein</subject><subject>Chromatography</subject><subject>cytokines</subject><subject>Cytokines - immunology</subject><subject>Cytokines - metabolism</subject><subject>Disease control</subject><subject>Disease Models, Animal</subject><subject>Effectiveness</subject><subject>Effector cells</subject><subject>Epitopes</subject><subject>Epitopes, T-Lymphocyte - immunology</subject><subject>Etiology</subject><subject>Female</subject><subject>Fusion protein</subject><subject>Immunization</subject><subject>Immunoglobulin G</subject><subject>Immunoinformatics</subject><subject>Immunologic Memory</subject><subject>Immunological memory</subject><subject>Immunology</subject><subject>Immunoprophylaxis</subject><subject>Leishmania amazonensis</subject><subject>Leishmania braziliensis - immunology</subject><subject>leishmaniasis</subject><subject>Leishmaniasis Vaccines - immunology</subject><subject>Leishmaniasis, Cutaneous - immunology</subject><subject>Leishmaniasis, Cutaneous - prevention & control</subject><subject>Lesions</subject><subject>Lipid A - analogs & derivatives</subject><subject>Lipid A - immunology</subject><subject>Lymphocytes</subject><subject>Lymphocytes T</subject><subject>memory</subject><subject>Memory cells</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Nitric oxide</subject><subject>nitrites</subject><subject>parasite load</subject><subject>Parasites</subject><subject>Parasitic diseases</subject><subject>Proteins</subject><subject>Protozoa</subject><subject>Public health</subject><subject>Reagents</subject><subject>recombinant fusion proteins</subject><subject>Recombinant Fusion Proteins - genetics</subject><subject>Recombinant Fusion Proteins - immunology</subject><subject>Skin diseases</subject><subject>Skin lesions</subject><subject>T-cell epitope mapping</subject><subject>Tegumentary leishmaniasis</subject><subject>Toxicity</subject><subject>Tumor necrosis factor-α</subject><subject>Vaccine</subject><subject>Vaccines</subject><subject>Vector-borne diseases</subject><subject>γ-Interferon</subject><issn>0264-410X</issn><issn>1873-2518</issn><issn>1873-2518</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</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>eNqFks-O0zAQxiMEYsvCI4AscVlplWIntmOfUNXln1QEhyJxs1xn0rqK7RI7hb4mT4S7KRy47MmH-X3zzYy_onhJ8Jxgwt_s50dtjPUwr3BF56TipBGPihkRTV1WjIjHxQxXnJaU4O9XxbMY9xhjVhP5tLiqJZa84WxW_F7e0VukfYuWd-IWrUsDfY_c2CdbwsGmcABkdtbBYA06DCGB9UjHGIzVCVr006ZdlqPPX1cLpNv9eNQ-Ievb0cDEm2SPgKDrrNHmdG_VB78tEwwOWedGH_qwzcVsCy4MJ9SFAaUdXIq5yWF36vUvG1Ho0OJ-lOy4hu3owCedFSuwcee0tzra-Lx40uk-wovLe118e_9uvfxYrr58-LRcrEpTY5pKyrnkAiTrKAHZipbUQHRVYy0M2TRMd42EDgxjIKXcUCIFiI1usOA1Z7yur4ubqW-e8McIMSln4_l82kMYo6oJoxVtJGcPo1g0XAra8Iy-_g_dh3HweZFMSVo3hLMmU2yizBBiHKBTh8G6fApFsDrnQ-3VJR_qnA815SPrXl26jxsH7T_V30Bk4O0EQL7c0cKgorHgDbR2yF-p2mAfsPgDwRjRbw</recordid><startdate>20240830</startdate><enddate>20240830</enddate><creator>Moura, Dênia Monteiro de</creator><creator>Carvalho, Ana Maria Ravena Severino</creator><creator>Brito, Rory Cristiane Fortes de</creator><creator>Roatt, Bruno Mendes</creator><creator>Lage, Daniela Pagliara</creator><creator>Martins, Vivian Tamietti</creator><creator>Cruz, Luiza dos Reis</creator><creator>Medeiros, Fernanda Alvarenga Cardoso</creator><creator>Batista, Sarah Dutra</creator><creator>Pinheiro, Guilherme Rafael Gomide</creator><creator>da Costa Rocha, Manoel Otávio</creator><creator>Coelho, Eduardo Antonio Ferraz</creator><creator>Duarte, Mariana Costa</creator><creator>Mendes, Tiago Antônio de Oliveira</creator><creator>Menezes-Souza, Daniel</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>AEUYN</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><scope>7S9</scope><scope>L.6</scope></search><sort><creationdate>20240830</creationdate><title>CD4+ and CD8+ T-cell multi-epitope chimeric protein associated with an MPLA adjuvant induce protective efficacy and long-term immunological memory for the immunoprophylaxis of American Tegumentary Leishmaniasis</title><author>Moura, Dênia Monteiro de ; Carvalho, Ana Maria Ravena Severino ; Brito, Rory Cristiane Fortes de ; Roatt, Bruno Mendes ; Lage, Daniela Pagliara ; Martins, Vivian Tamietti ; Cruz, Luiza dos Reis ; Medeiros, Fernanda Alvarenga Cardoso ; Batista, Sarah Dutra ; Pinheiro, Guilherme Rafael Gomide ; da Costa Rocha, Manoel Otávio ; Coelho, Eduardo Antonio Ferraz ; Duarte, Mariana Costa ; Mendes, Tiago Antônio de Oliveira ; Menezes-Souza, Daniel</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c304t-466968e95f41e9d8d13e1a230a8c1b75af79efec55e999b4198e8ba7086365633</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Adjuvants</topic><topic>Adjuvants, Immunologic - administration & dosage</topic><topic>American Tegumentary Leishmaniasis</topic><topic>Animal models</topic><topic>Animals</topic><topic>Antibodies, Protozoan - immunology</topic><topic>Antigens</topic><topic>Antigens, Protozoan - immunology</topic><topic>Brazil</topic><topic>CD4 antigen</topic><topic>CD4-Positive T-Lymphocytes - immunology</topic><topic>CD8 antigen</topic><topic>CD8-positive T-lymphocytes</topic><topic>CD8-Positive T-Lymphocytes - immunology</topic><topic>Cell fusion</topic><topic>Chimeric protein</topic><topic>Chromatography</topic><topic>cytokines</topic><topic>Cytokines - immunology</topic><topic>Cytokines - metabolism</topic><topic>Disease control</topic><topic>Disease Models, Animal</topic><topic>Effectiveness</topic><topic>Effector cells</topic><topic>Epitopes</topic><topic>Epitopes, T-Lymphocyte - immunology</topic><topic>Etiology</topic><topic>Female</topic><topic>Fusion protein</topic><topic>Immunization</topic><topic>Immunoglobulin G</topic><topic>Immunoinformatics</topic><topic>Immunologic Memory</topic><topic>Immunological memory</topic><topic>Immunology</topic><topic>Immunoprophylaxis</topic><topic>Leishmania amazonensis</topic><topic>Leishmania braziliensis - immunology</topic><topic>leishmaniasis</topic><topic>Leishmaniasis Vaccines - immunology</topic><topic>Leishmaniasis, Cutaneous - immunology</topic><topic>Leishmaniasis, Cutaneous - prevention & control</topic><topic>Lesions</topic><topic>Lipid A - analogs & derivatives</topic><topic>Lipid A - immunology</topic><topic>Lymphocytes</topic><topic>Lymphocytes T</topic><topic>memory</topic><topic>Memory cells</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Nitric oxide</topic><topic>nitrites</topic><topic>parasite load</topic><topic>Parasites</topic><topic>Parasitic diseases</topic><topic>Proteins</topic><topic>Protozoa</topic><topic>Public health</topic><topic>Reagents</topic><topic>recombinant fusion proteins</topic><topic>Recombinant Fusion Proteins - genetics</topic><topic>Recombinant Fusion Proteins - immunology</topic><topic>Skin diseases</topic><topic>Skin lesions</topic><topic>T-cell epitope mapping</topic><topic>Tegumentary leishmaniasis</topic><topic>Toxicity</topic><topic>Tumor necrosis factor-α</topic><topic>Vaccine</topic><topic>Vaccines</topic><topic>Vector-borne diseases</topic><topic>γ-Interferon</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Moura, Dênia Monteiro de</creatorcontrib><creatorcontrib>Carvalho, Ana Maria Ravena Severino</creatorcontrib><creatorcontrib>Brito, Rory Cristiane Fortes de</creatorcontrib><creatorcontrib>Roatt, Bruno Mendes</creatorcontrib><creatorcontrib>Lage, Daniela Pagliara</creatorcontrib><creatorcontrib>Martins, Vivian Tamietti</creatorcontrib><creatorcontrib>Cruz, Luiza dos Reis</creatorcontrib><creatorcontrib>Medeiros, Fernanda Alvarenga Cardoso</creatorcontrib><creatorcontrib>Batista, Sarah Dutra</creatorcontrib><creatorcontrib>Pinheiro, Guilherme Rafael Gomide</creatorcontrib><creatorcontrib>da Costa Rocha, Manoel Otávio</creatorcontrib><creatorcontrib>Coelho, Eduardo Antonio Ferraz</creatorcontrib><creatorcontrib>Duarte, Mariana Costa</creatorcontrib><creatorcontrib>Mendes, Tiago Antônio de Oliveira</creatorcontrib><creatorcontrib>Menezes-Souza, Daniel</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 One Sustainability</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 (ProQuest)</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><collection>AGRICOLA</collection><collection>AGRICOLA - Academic</collection><jtitle>Vaccine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Moura, Dênia Monteiro de</au><au>Carvalho, Ana Maria Ravena Severino</au><au>Brito, Rory Cristiane Fortes de</au><au>Roatt, Bruno Mendes</au><au>Lage, Daniela Pagliara</au><au>Martins, Vivian Tamietti</au><au>Cruz, Luiza dos Reis</au><au>Medeiros, Fernanda Alvarenga Cardoso</au><au>Batista, Sarah Dutra</au><au>Pinheiro, Guilherme Rafael Gomide</au><au>da Costa Rocha, Manoel Otávio</au><au>Coelho, Eduardo Antonio Ferraz</au><au>Duarte, Mariana Costa</au><au>Mendes, Tiago Antônio de Oliveira</au><au>Menezes-Souza, Daniel</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>CD4+ and CD8+ T-cell multi-epitope chimeric protein associated with an MPLA adjuvant induce protective efficacy and long-term immunological memory for the immunoprophylaxis of American Tegumentary Leishmaniasis</atitle><jtitle>Vaccine</jtitle><addtitle>Vaccine</addtitle><date>2024-08-30</date><risdate>2024</risdate><volume>42</volume><issue>21</issue><spage>126178</spage><pages>126178-</pages><artnum>126178</artnum><issn>0264-410X</issn><issn>1873-2518</issn><eissn>1873-2518</eissn><abstract>American Tegumentary Leishmaniasis (ATL) is a disease of high severity and incidence in Brazil, in addition to being a worldwide concern in public health. Leishmania amazonensis is one of the etiological agents of ATL, and the inefficiency of control measures, associated with the high toxicity of the treatment and the lack of effective immunoprophylactic strategies, makes the development of vaccines indispensable and imminent. In this light, the present study proposes to elaborate a chimeric protein (rChiP), based on the fusion of multiple epitopes of CD4+/CD8+ T cells, identified in the immunoproteome of the parasites L. amazonensis and L. braziliensis. The designed chimeric protein was tested in the L. amazonensis murine model of infection using the following formulations: 25 μg of the rChiP in saline (rChiP group) and 25 μg of the rChiP plus 25 μg of MPLA-PHAD® (rChiP+MPLA group). After completing immunization, CD4+ and CD8+ T cells, stimulated with SLa-Antigen or rChiP, showed an increased production of nitric oxide and intracytoplasmic pro-inflammatory cytokines, in addition to the generation of central and effector memory T cells. rChiP and rChiP+MPLA formulations were able to promote an effective protection against L. amazonensis infection determined by a reduction in the development of skin lesions and lower parasitic burden. Reduction in the development of skin lesions and lower parasitic burden in the vaccinated groups were associated with an increase of nitrite, CD4+/CD8+IFN-γ+TNF-α+ and CD4+/CD8+CD44highCD62Lhigh/low T cells, IgGTotal, IgG2a, and lower rates of IgG1 and CD4+/CD8+IL-10+. This data suggests that proposed formulations could be considered potential tools to prevent ATL.
[Display omitted]
•Rational strategy to develop antigens.•Integration between immunoproteomic and immunoinformatics analyses.•Chimeric protein shows high performance in ATL diagnosis.</abstract><cop>Netherlands</cop><pub>Elsevier Ltd</pub><pmid>39096765</pmid><doi>10.1016/j.vaccine.2024.126178</doi></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0264-410X |
| ispartof | Vaccine, 2024-08, Vol.42 (21), p.126178, Article 126178 |
| issn | 0264-410X 1873-2518 1873-2518 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_3154247965 |
| source | MEDLINE; ScienceDirect Journals (5 years ago - present); ProQuest Central UK/Ireland |
| subjects | Adjuvants Adjuvants, Immunologic - administration & dosage American Tegumentary Leishmaniasis Animal models Animals Antibodies, Protozoan - immunology Antigens Antigens, Protozoan - immunology Brazil CD4 antigen CD4-Positive T-Lymphocytes - immunology CD8 antigen CD8-positive T-lymphocytes CD8-Positive T-Lymphocytes - immunology Cell fusion Chimeric protein Chromatography cytokines Cytokines - immunology Cytokines - metabolism Disease control Disease Models, Animal Effectiveness Effector cells Epitopes Epitopes, T-Lymphocyte - immunology Etiology Female Fusion protein Immunization Immunoglobulin G Immunoinformatics Immunologic Memory Immunological memory Immunology Immunoprophylaxis Leishmania amazonensis Leishmania braziliensis - immunology leishmaniasis Leishmaniasis Vaccines - immunology Leishmaniasis, Cutaneous - immunology Leishmaniasis, Cutaneous - prevention & control Lesions Lipid A - analogs & derivatives Lipid A - immunology Lymphocytes Lymphocytes T memory Memory cells Mice Mice, Inbred BALB C Nitric oxide nitrites parasite load Parasites Parasitic diseases Proteins Protozoa Public health Reagents recombinant fusion proteins Recombinant Fusion Proteins - genetics Recombinant Fusion Proteins - immunology Skin diseases Skin lesions T-cell epitope mapping Tegumentary leishmaniasis Toxicity Tumor necrosis factor-α Vaccine Vaccines Vector-borne diseases γ-Interferon |
| title | CD4+ and CD8+ T-cell multi-epitope chimeric protein associated with an MPLA adjuvant induce protective efficacy and long-term immunological memory for the immunoprophylaxis of American Tegumentary Leishmaniasis |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-15T12%3A00%3A50IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=CD4+%20and%20CD8+%20T-cell%20multi-epitope%20chimeric%20protein%20associated%20with%20an%20MPLA%20adjuvant%20induce%20protective%20efficacy%20and%20long-term%20immunological%20memory%20for%20the%20immunoprophylaxis%20of%20American%20Tegumentary%20Leishmaniasis&rft.jtitle=Vaccine&rft.au=Moura,%20D%C3%AAnia%20Monteiro%20de&rft.date=2024-08-30&rft.volume=42&rft.issue=21&rft.spage=126178&rft.pages=126178-&rft.artnum=126178&rft.issn=0264-410X&rft.eissn=1873-2518&rft_id=info:doi/10.1016/j.vaccine.2024.126178&rft_dat=%3Cproquest_cross%3E3087698476%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=3094371657&rft_id=info:pmid/39096765&rft_els_id=S0264410X24008417&rfr_iscdi=true |