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.