Head-to-head comparison of three vaccination strategies based on DNA and raw insect-derived recombinant proteins against Leishmania.
Parasitic diseases plague billions of people among the poorest, killing millions annually, and causing additional millions of disability-adjusted life years lost. Leishmaniases affect more than 12 million people, with over 350 million people at risk. There is an urgent need for efficacious and cheap...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2012-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3517401?pdf=render |
| _version_ | 1818851388707307520 |
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| author | Felicitat Todolí Alhelí Rodríguez-Cortés María Del Carmen Núñez Márcia D Laurenti Silvia Gómez-Sebastián Fernando Rodríguez Eva Pérez-Martín José M Escribano Jordi Alberola |
| author_facet | Felicitat Todolí Alhelí Rodríguez-Cortés María Del Carmen Núñez Márcia D Laurenti Silvia Gómez-Sebastián Fernando Rodríguez Eva Pérez-Martín José M Escribano Jordi Alberola |
| author_sort | Felicitat Todolí |
| collection | DOAJ |
| description | Parasitic diseases plague billions of people among the poorest, killing millions annually, and causing additional millions of disability-adjusted life years lost. Leishmaniases affect more than 12 million people, with over 350 million people at risk. There is an urgent need for efficacious and cheap vaccines and treatments against visceral leishmaniasis (VL), its most severe form. Several vaccination strategies have been proposed but to date no head-to-head comparison was undertaken to assess which is the best in a clinical model of the disease. We simultaneously assayed three vaccination strategies against VL in the hamster model, using KMPII, TRYP, LACK, and PAPLE22 vaccine candidate antigens. Four groups of hamsters were immunized using the following approaches: 1) raw extracts of baculovirus-infected Trichoplusia ni larvae expressing individually one of the four recombinant proteins (PROT); 2) naked pVAX1 plasmids carrying the four genes individually (DNA); 3) a heterologous prime-boost (HPB) strategy involving DNA followed by PROT (DNA-PROT); and 4) a Control including empty pVAX1 plasmid followed by raw extract of wild-type baculovirus-infected T. ni larvae. Hamsters were challenged with L. infantum promastigotes and maintained for 20 weeks. While PROT vaccine was not protective, DNA vaccination achieved protection in spleen. Only DNA-PROT vaccination induced significant NO production by macrophages, accompanied by a significant parasitological protection in spleen and blood. Thus, the DNA-PROT strategy elicits strong immune responses and high parasitological protection in the clinical model of VL, better than its corresponding naked DNA or protein versions. Furthermore, we show that naked DNA coupled with raw recombinant proteins produced in insect larvae biofactories -the cheapest way of producing DNA-PROT vaccines- is a practical and cost-effective way for potential "off the shelf" supplying vaccines at very low prices for the protection against leishmaniases, and possibly against other parasitic diseases affecting the poorest of the poor. |
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| format | Article |
| id | doaj.art-f765df0972784e4cbb8167c1b8d1d0df |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-19T07:04:14Z |
| publishDate | 2012-01-01 |
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| spelling | doaj.art-f765df0972784e4cbb8167c1b8d1d0df2022-12-21T20:31:20ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-01712e5118110.1371/journal.pone.0051181Head-to-head comparison of three vaccination strategies based on DNA and raw insect-derived recombinant proteins against Leishmania.Felicitat TodolíAlhelí Rodríguez-CortésMaría Del Carmen NúñezMárcia D LaurentiSilvia Gómez-SebastiánFernando RodríguezEva Pérez-MartínJosé M EscribanoJordi AlberolaParasitic diseases plague billions of people among the poorest, killing millions annually, and causing additional millions of disability-adjusted life years lost. Leishmaniases affect more than 12 million people, with over 350 million people at risk. There is an urgent need for efficacious and cheap vaccines and treatments against visceral leishmaniasis (VL), its most severe form. Several vaccination strategies have been proposed but to date no head-to-head comparison was undertaken to assess which is the best in a clinical model of the disease. We simultaneously assayed three vaccination strategies against VL in the hamster model, using KMPII, TRYP, LACK, and PAPLE22 vaccine candidate antigens. Four groups of hamsters were immunized using the following approaches: 1) raw extracts of baculovirus-infected Trichoplusia ni larvae expressing individually one of the four recombinant proteins (PROT); 2) naked pVAX1 plasmids carrying the four genes individually (DNA); 3) a heterologous prime-boost (HPB) strategy involving DNA followed by PROT (DNA-PROT); and 4) a Control including empty pVAX1 plasmid followed by raw extract of wild-type baculovirus-infected T. ni larvae. Hamsters were challenged with L. infantum promastigotes and maintained for 20 weeks. While PROT vaccine was not protective, DNA vaccination achieved protection in spleen. Only DNA-PROT vaccination induced significant NO production by macrophages, accompanied by a significant parasitological protection in spleen and blood. Thus, the DNA-PROT strategy elicits strong immune responses and high parasitological protection in the clinical model of VL, better than its corresponding naked DNA or protein versions. Furthermore, we show that naked DNA coupled with raw recombinant proteins produced in insect larvae biofactories -the cheapest way of producing DNA-PROT vaccines- is a practical and cost-effective way for potential "off the shelf" supplying vaccines at very low prices for the protection against leishmaniases, and possibly against other parasitic diseases affecting the poorest of the poor.http://europepmc.org/articles/PMC3517401?pdf=render |
| spellingShingle | Felicitat Todolí Alhelí Rodríguez-Cortés María Del Carmen Núñez Márcia D Laurenti Silvia Gómez-Sebastián Fernando Rodríguez Eva Pérez-Martín José M Escribano Jordi Alberola Head-to-head comparison of three vaccination strategies based on DNA and raw insect-derived recombinant proteins against Leishmania. PLoS ONE |
| title | Head-to-head comparison of three vaccination strategies based on DNA and raw insect-derived recombinant proteins against Leishmania. |
| title_full | Head-to-head comparison of three vaccination strategies based on DNA and raw insect-derived recombinant proteins against Leishmania. |
| title_fullStr | Head-to-head comparison of three vaccination strategies based on DNA and raw insect-derived recombinant proteins against Leishmania. |
| title_full_unstemmed | Head-to-head comparison of three vaccination strategies based on DNA and raw insect-derived recombinant proteins against Leishmania. |
| title_short | Head-to-head comparison of three vaccination strategies based on DNA and raw insect-derived recombinant proteins against Leishmania. |
| title_sort | head to head comparison of three vaccination strategies based on dna and raw insect derived recombinant proteins against leishmania |
| url | http://europepmc.org/articles/PMC3517401?pdf=render |
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