title: Head-to-head comparison of three vaccination strategies based on DNA and raw insect-derived recombinant proteins against Leishmania.
abstract: 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.
authors.affiliation: LeishLAB-Servei d'Anàlisi de Fàrmacs, Departament de Farmacologia, de Terapèutica i de Toxicologia, Edifici V, Universitat Autònoma de Barcelona, Bellaterra, Barcelona, Spain.
authors.forename: Felicitat
authors.initials: F
authors.lastname: Todolí
authors.forename: Alhelí
authors.initials: A
authors.lastname: Rodríguez-Cortés
authors.forename: María Del Carmen
authors.initials: Mdel C
authors.lastname: Núñez
authors.forename: Márcia D
authors.initials: MD
authors.lastname: Laurenti
authors.forename: Silvia
authors.initials: S
authors.lastname: Gómez-Sebastián
authors.forename: Fernando
authors.initials: F
authors.lastname: Rodríguez
authors.forename: Eva
authors.initials: E
authors.lastname: Pérez-Martín
authors.forename: José M
authors.initials: JM
authors.lastname: Escribano
authors.forename: Jordi
authors.initials: J
authors.lastname: Alberola
mesh_terms: D000818:Animals; D000956:Antigens, Viral / Q000276:immunology; D006224:Cricetinae; D004247:DNA / Q000276:immunology*; D006801:Humans; D007891:Leishmania / Q000276:immunology*; D007896:Leishmaniasis / Q000473:pathology / Q000517:prevention & control*; D009036:Moths / Q000378:metabolism; D010957:Plasmids / Q000235:genetics; D011994:Recombinant Proteins / Q000276:immunology*; D018709:Statistics, Nonparametric; D014611:Vaccination / Q000379:methods*
chemical_list: D000956:Antigens, Viral; D011994:Recombinant Proteins; D004247:DNA