A chimeric vaccine combined with adjuvant system induces immunogenicity and protection against visceral leishmaniasis in BALB/c mice
In Brazil, canine visceral leishmaniasis is an important public health problem due to its alarming growth. The high prevalence of infected dogs reinforces the need for a vaccine for use in prophylactic vaccination campaigns. In the present study, we evaluate the immunogenicity and protection of the...
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| Veröffentlicht in: | Vaccine 2021-05, Vol.39 (20), p.2755-2763 |
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| creator | Ostolin, Thais Lopes Valentim Di Paschoale Gusmão, Miriã Rodrigues Mathias, Fernando Augusto Siqueira Cardoso, Jamille Mirelle de Oliveira Roatt, Bruno Mendes Aguiar-Soares, Rodrigo Dian de Oliveira Ruiz, Jeronimo Conceição Resende, Daniela de Melo de Brito, Rory Cristiane Fortes Reis, Alexandre Barbosa |
| description | In Brazil, canine visceral leishmaniasis is an important public health problem due to its alarming growth. The high prevalence of infected dogs reinforces the need for a vaccine for use in prophylactic vaccination campaigns. In the present study, we evaluate the immunogenicity and protection of the best dose of Chimera A selected through the screening of cytokines production important in disease. BALB/c mice were vaccinated subcutaneously with three doses and challenged intravenously with 1 × 107L. infantum promastigotes. Spleen samples were collected to assess the intracellular cytokine profile production, T cell proliferation and parasite load. At first, three different doses of Chimera A (5 μg, 10 μg and 20 μg) were evaluated through the production of IFN-γ and IL-10 cytokines. Since the dose of 20 μg showed the best results, it was chosen to continue the study. Secondarily, Chimera A at dose of 20 μg was formulated with Saponin plus Monophosphoryl lipid A. Vaccination with Chimera A alone and formulated with SM adjuvant system was able to increase the percentage of the proliferation of specific T lymphocytes and stimulated a Th1 response with increased levels of IFN-γ, TNF-α and IL-2, and decreased of IL-4 and IL-10. The vaccine efficacy through real-time PCR demonstrated a reduction in the splenic parasite load in animals that received Chimera A formulated with the SM adjuvant system (92%). Additionally, we observed increased levels of nitric oxide in stimulated-culture supernatants. The Chimera A formulated with the SM adjuvant system was potentially immunogenic, being able to induce immunoprotective mechanisms and reduce parasite load. Therefore, the use of T-cell multi-epitope vaccine is promising against visceral leishmaniasis. |
| doi_str_mv | 10.1016/j.vaccine.2021.04.004 |
| format | Article |
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The high prevalence of infected dogs reinforces the need for a vaccine for use in prophylactic vaccination campaigns. In the present study, we evaluate the immunogenicity and protection of the best dose of Chimera A selected through the screening of cytokines production important in disease. BALB/c mice were vaccinated subcutaneously with three doses and challenged intravenously with 1 × 107L. infantum promastigotes. Spleen samples were collected to assess the intracellular cytokine profile production, T cell proliferation and parasite load. At first, three different doses of Chimera A (5 μg, 10 μg and 20 μg) were evaluated through the production of IFN-γ and IL-10 cytokines. Since the dose of 20 μg showed the best results, it was chosen to continue the study. Secondarily, Chimera A at dose of 20 μg was formulated with Saponin plus Monophosphoryl lipid A. Vaccination with Chimera A alone and formulated with SM adjuvant system was able to increase the percentage of the proliferation of specific T lymphocytes and stimulated a Th1 response with increased levels of IFN-γ, TNF-α and IL-2, and decreased of IL-4 and IL-10. The vaccine efficacy through real-time PCR demonstrated a reduction in the splenic parasite load in animals that received Chimera A formulated with the SM adjuvant system (92%). Additionally, we observed increased levels of nitric oxide in stimulated-culture supernatants. The Chimera A formulated with the SM adjuvant system was potentially immunogenic, being able to induce immunoprotective mechanisms and reduce parasite load. Therefore, the use of T-cell multi-epitope vaccine is promising against visceral leishmaniasis.</description><identifier>ISSN: 0264-410X</identifier><identifier>EISSN: 1873-2518</identifier><identifier>DOI: 10.1016/j.vaccine.2021.04.004</identifier><identifier>PMID: 33875268</identifier><language>eng</language><publisher>Netherlands: Elsevier Ltd</publisher><subject>Adjuvants ; Adjuvants, Immunologic ; Animals ; Antigens ; Antigens, Protozoan ; BALB/c ; Brazil ; Cell culture ; Cell growth ; Cell proliferation ; Chimera ; Cloning ; Combined vaccines ; Cytokines ; Data analysis ; Dogs ; Epitopes ; Evaluation ; Flow cytometry ; Immune response ; Immunogenicity ; Interleukin 10 ; Interleukin 2 ; Interleukin 4 ; Leishmania infantum ; Leishmaniasis Vaccines ; Leishmaniasis, Visceral - prevention & control ; Lipid A ; Lipids ; Lymphocytes ; Lymphocytes T ; Mice ; Mice, Inbred BALB C ; Monophosphoryl lipid A ; Multi-epitope vaccine ; Nitric oxide ; Parasites ; Parasitic diseases ; Peptides ; Promastigotes ; Proteins ; Public health ; Saponins ; Spleen ; Tumor necrosis factor-α ; Vaccination ; Vaccine efficacy ; Vaccines ; Vector-borne diseases ; Visceral leishmaniasis ; γ-Interferon</subject><ispartof>Vaccine, 2021-05, Vol.39 (20), p.2755-2763</ispartof><rights>2021 Elsevier Ltd</rights><rights>Copyright © 2021 Elsevier Ltd. All rights reserved.</rights><rights>2021. Elsevier Ltd</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c440t-d0b7d17cbf7bd81cdd6b1245395262b3b9150169f627a67a4280388b1b225f2c3</citedby><cites>FETCH-LOGICAL-c440t-d0b7d17cbf7bd81cdd6b1245395262b3b9150169f627a67a4280388b1b225f2c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.proquest.com/docview/2519292839?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>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33875268$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ostolin, Thais Lopes Valentim Di Paschoale</creatorcontrib><creatorcontrib>Gusmão, Miriã Rodrigues</creatorcontrib><creatorcontrib>Mathias, Fernando Augusto Siqueira</creatorcontrib><creatorcontrib>Cardoso, Jamille Mirelle de Oliveira</creatorcontrib><creatorcontrib>Roatt, Bruno Mendes</creatorcontrib><creatorcontrib>Aguiar-Soares, Rodrigo Dian de Oliveira</creatorcontrib><creatorcontrib>Ruiz, Jeronimo Conceição</creatorcontrib><creatorcontrib>Resende, Daniela de Melo</creatorcontrib><creatorcontrib>de Brito, Rory Cristiane Fortes</creatorcontrib><creatorcontrib>Reis, Alexandre Barbosa</creatorcontrib><title>A chimeric vaccine combined with adjuvant system induces immunogenicity and protection against visceral leishmaniasis in BALB/c mice</title><title>Vaccine</title><addtitle>Vaccine</addtitle><description>In Brazil, canine visceral leishmaniasis is an important public health problem due to its alarming growth. The high prevalence of infected dogs reinforces the need for a vaccine for use in prophylactic vaccination campaigns. In the present study, we evaluate the immunogenicity and protection of the best dose of Chimera A selected through the screening of cytokines production important in disease. BALB/c mice were vaccinated subcutaneously with three doses and challenged intravenously with 1 × 107L. infantum promastigotes. Spleen samples were collected to assess the intracellular cytokine profile production, T cell proliferation and parasite load. At first, three different doses of Chimera A (5 μg, 10 μg and 20 μg) were evaluated through the production of IFN-γ and IL-10 cytokines. Since the dose of 20 μg showed the best results, it was chosen to continue the study. Secondarily, Chimera A at dose of 20 μg was formulated with Saponin plus Monophosphoryl lipid A. Vaccination with Chimera A alone and formulated with SM adjuvant system was able to increase the percentage of the proliferation of specific T lymphocytes and stimulated a Th1 response with increased levels of IFN-γ, TNF-α and IL-2, and decreased of IL-4 and IL-10. The vaccine efficacy through real-time PCR demonstrated a reduction in the splenic parasite load in animals that received Chimera A formulated with the SM adjuvant system (92%). Additionally, we observed increased levels of nitric oxide in stimulated-culture supernatants. The Chimera A formulated with the SM adjuvant system was potentially immunogenic, being able to induce immunoprotective mechanisms and reduce parasite load. Therefore, the use of T-cell multi-epitope vaccine is promising against visceral leishmaniasis.</description><subject>Adjuvants</subject><subject>Adjuvants, Immunologic</subject><subject>Animals</subject><subject>Antigens</subject><subject>Antigens, Protozoan</subject><subject>BALB/c</subject><subject>Brazil</subject><subject>Cell culture</subject><subject>Cell growth</subject><subject>Cell proliferation</subject><subject>Chimera</subject><subject>Cloning</subject><subject>Combined vaccines</subject><subject>Cytokines</subject><subject>Data analysis</subject><subject>Dogs</subject><subject>Epitopes</subject><subject>Evaluation</subject><subject>Flow cytometry</subject><subject>Immune response</subject><subject>Immunogenicity</subject><subject>Interleukin 10</subject><subject>Interleukin 2</subject><subject>Interleukin 4</subject><subject>Leishmania infantum</subject><subject>Leishmaniasis Vaccines</subject><subject>Leishmaniasis, Visceral - prevention & control</subject><subject>Lipid 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chimeric vaccine combined with adjuvant system induces immunogenicity and protection against visceral leishmaniasis in BALB/c mice</title><author>Ostolin, Thais Lopes Valentim Di Paschoale ; Gusmão, Miriã Rodrigues ; Mathias, Fernando Augusto Siqueira ; Cardoso, Jamille Mirelle de Oliveira ; Roatt, Bruno Mendes ; Aguiar-Soares, Rodrigo Dian de Oliveira ; Ruiz, Jeronimo Conceição ; Resende, Daniela de Melo ; de Brito, Rory Cristiane Fortes ; Reis, Alexandre Barbosa</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c440t-d0b7d17cbf7bd81cdd6b1245395262b3b9150169f627a67a4280388b1b225f2c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Adjuvants</topic><topic>Adjuvants, Immunologic</topic><topic>Animals</topic><topic>Antigens</topic><topic>Antigens, Protozoan</topic><topic>BALB/c</topic><topic>Brazil</topic><topic>Cell culture</topic><topic>Cell growth</topic><topic>Cell proliferation</topic><topic>Chimera</topic><topic>Cloning</topic><topic>Combined vaccines</topic><topic>Cytokines</topic><topic>Data analysis</topic><topic>Dogs</topic><topic>Epitopes</topic><topic>Evaluation</topic><topic>Flow cytometry</topic><topic>Immune response</topic><topic>Immunogenicity</topic><topic>Interleukin 10</topic><topic>Interleukin 2</topic><topic>Interleukin 4</topic><topic>Leishmania infantum</topic><topic>Leishmaniasis Vaccines</topic><topic>Leishmaniasis, Visceral - prevention & control</topic><topic>Lipid A</topic><topic>Lipids</topic><topic>Lymphocytes</topic><topic>Lymphocytes T</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Monophosphoryl lipid A</topic><topic>Multi-epitope vaccine</topic><topic>Nitric oxide</topic><topic>Parasites</topic><topic>Parasitic diseases</topic><topic>Peptides</topic><topic>Promastigotes</topic><topic>Proteins</topic><topic>Public health</topic><topic>Saponins</topic><topic>Spleen</topic><topic>Tumor necrosis 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mice</atitle><jtitle>Vaccine</jtitle><addtitle>Vaccine</addtitle><date>2021-05-12</date><risdate>2021</risdate><volume>39</volume><issue>20</issue><spage>2755</spage><epage>2763</epage><pages>2755-2763</pages><issn>0264-410X</issn><eissn>1873-2518</eissn><abstract>In Brazil, canine visceral leishmaniasis is an important public health problem due to its alarming growth. The high prevalence of infected dogs reinforces the need for a vaccine for use in prophylactic vaccination campaigns. In the present study, we evaluate the immunogenicity and protection of the best dose of Chimera A selected through the screening of cytokines production important in disease. BALB/c mice were vaccinated subcutaneously with three doses and challenged intravenously with 1 × 107L. infantum promastigotes. Spleen samples were collected to assess the intracellular cytokine profile production, T cell proliferation and parasite load. At first, three different doses of Chimera A (5 μg, 10 μg and 20 μg) were evaluated through the production of IFN-γ and IL-10 cytokines. Since the dose of 20 μg showed the best results, it was chosen to continue the study. Secondarily, Chimera A at dose of 20 μg was formulated with Saponin plus Monophosphoryl lipid A. Vaccination with Chimera A alone and formulated with SM adjuvant system was able to increase the percentage of the proliferation of specific T lymphocytes and stimulated a Th1 response with increased levels of IFN-γ, TNF-α and IL-2, and decreased of IL-4 and IL-10. The vaccine efficacy through real-time PCR demonstrated a reduction in the splenic parasite load in animals that received Chimera A formulated with the SM adjuvant system (92%). Additionally, we observed increased levels of nitric oxide in stimulated-culture supernatants. The Chimera A formulated with the SM adjuvant system was potentially immunogenic, being able to induce immunoprotective mechanisms and reduce parasite load. Therefore, the use of T-cell multi-epitope vaccine is promising against visceral leishmaniasis.</abstract><cop>Netherlands</cop><pub>Elsevier Ltd</pub><pmid>33875268</pmid><doi>10.1016/j.vaccine.2021.04.004</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0264-410X |
| ispartof | Vaccine, 2021-05, Vol.39 (20), p.2755-2763 |
| issn | 0264-410X 1873-2518 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_2515685741 |
| source | MEDLINE; Access via ScienceDirect (Elsevier); ProQuest Central UK/Ireland |
| subjects | Adjuvants Adjuvants, Immunologic Animals Antigens Antigens, Protozoan BALB/c Brazil Cell culture Cell growth Cell proliferation Chimera Cloning Combined vaccines Cytokines Data analysis Dogs Epitopes Evaluation Flow cytometry Immune response Immunogenicity Interleukin 10 Interleukin 2 Interleukin 4 Leishmania infantum Leishmaniasis Vaccines Leishmaniasis, Visceral - prevention & control Lipid A Lipids Lymphocytes Lymphocytes T Mice Mice, Inbred BALB C Monophosphoryl lipid A Multi-epitope vaccine Nitric oxide Parasites Parasitic diseases Peptides Promastigotes Proteins Public health Saponins Spleen Tumor necrosis factor-α Vaccination Vaccine efficacy Vaccines Vector-borne diseases Visceral leishmaniasis γ-Interferon |
| title | A chimeric vaccine combined with adjuvant system induces immunogenicity and protection against visceral leishmaniasis in BALB/c mice |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-19T15%3A57%3A22IST&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=A%20chimeric%20vaccine%20combined%20with%20adjuvant%20system%20induces%20immunogenicity%20and%20protection%20against%20visceral%20leishmaniasis%20in%20BALB/c%20mice&rft.jtitle=Vaccine&rft.au=Ostolin,%20Thais%20Lopes%20Valentim%20Di%20Paschoale&rft.date=2021-05-12&rft.volume=39&rft.issue=20&rft.spage=2755&rft.epage=2763&rft.pages=2755-2763&rft.issn=0264-410X&rft.eissn=1873-2518&rft_id=info:doi/10.1016/j.vaccine.2021.04.004&rft_dat=%3Cproquest_cross%3E2519292839%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=2519292839&rft_id=info:pmid/33875268&rft_els_id=S0264410X21004291&rfr_iscdi=true |