HisAK70: Progress towards a vaccine against different forms of leishmaniosis

Background: Leishmania major and Leishmania infantum are among the main species that are responsible for cutaneous leishmaniosis (CL) and visceral leishmaniosis (VL), respectively. The leishmanioses represent the second-largest parasitic killer in the world after malaria. Recently, we succeeded in generating a plasmid DNA (pCMV-HISA70m2A) and demonstrated that immunized mice were protected against L. major challenge. The efficacy of the DNA-vaccine was further enhanced by the inclusion of KMP-11 antigen into the antibiotic-free plasmid pVAX1-asd. Methods: Here, we describe the use of a HisAK70 DNA-vaccine encoding seven Leishmania genes (H2A, H2B, H3, H4, A2, KMP11 and HSP70) for vaccination of mice to assess the induction of a resistant phenotype against VL and CL. Results: HisAK70 was successful in vaccinated mice, resulting in a high amount of efficient sterile hepatic granulomas associated with a hepatic parasite burden fully resolved in the VL model; and resulting in 100 % inhibition of parasite visceralization in the CL model. Conclusions: The results suggest that immunization with the HisAK70 DNA-vaccine may provide a rapid, suitable, and efficient vaccination strategy to confer cross-protective immunity against VL and CL.This work was partially supported by grants from the Spanish Ministry of Economy and Competitiveness (AGL2010-17394 and AGL2013-44100R) and PLATESA (P2013/ABI-2906) from the Comunidad de Madrid (Spain).Peer Reviewe

Antigenic extracts of Leishmania braziliensis and Leishmania amazonensis associated with saponin partially protects BALB/c mice against Leishmania chagasi infection by suppressing IL-10 and IL-4 production

This study evaluated two vaccine candidates for their effectiveness in protecting BALB/c mice against Leishmania chagasiinfection. These immunogenic preparations were composed of Leishmania amazonensisor Leishmania braziliensisantigenic extracts in association with saponin adjuvant. Mice were given three subcutaneous doses of one of these vaccine candidates weekly for three weeks and four weeks later challenged with promastigotes of L. chagasiby intravenous injection. We observed that both vaccine candidates induced a significant reduction in the parasite load of the liver, while the L. amazonensisantigenic extract also stimulated a reduction in spleen parasite load. This protection was associated with a suppression of both interleukin (IL)-10 and IL-4 cytokines by spleen cells in response to L. chagasiantigen. No change was detected in the production of IFN-γ. Our data show that these immunogenic preparations reduce the type 2 immune response leading to the control of parasite replication

Full-Mouth Ultrasonic Debridement Associated With Amoxicillin and Metronidazole in the Treatment of Severe Chronic Periodontitis

Background: The purpose of this study was to evaluate the adjunctive clinical, microbiologic, and immunologic effects of the systemic administration of amoxicillin and metronidazole in the full-mouth ultrasonic debridement of patients with severe chronic periodontitis. Methods: Twenty-five patients presenting at least eight teeth with probing depth (PD) 5 mm and bleeding on probing (BOP) were selected and randomly assigned to full-mouth ultrasonic debridement + placebo (control group) or full-mouth ultrasonic debridement + amoxicillin and metronidazole (test group). The clinical outcomes evaluated were visible plaque index, BOP, position of the gingival margin, relative attachment level (RAL), and PD. Real-time polymerase chain reaction (PCR) was used for quantitative analysis of Aggregatibacter actinomycetemcomitans (previously Actinobacillus actinomycetemcomitans), Porphyromonas gingivalis, and Tannerella forsythia (previously T forsythensis). The enzyme-linked immunosorbent assay (ELISA) technique permitted the detection of prostaglandin E(2), interleukin-1 beta, and interferon-gamma levels in gingival crevicular fluid. All parameters were evaluated at baseline and at 3 and 6 months post-treatment. Results: At 6 months, the test treatment resulted in lower BOP and an additional reduction (0.83 mm) in PD (P= 2 mm at 43.52% of sites in control patients compared to 58.03% of sites in test patients (P= 5 mm exhibiting RAL gain >= 2 mm in the test group. Nevertheless, no improvement in the microbiologic or immunologic outcome was observed with the adjunctive use of systemic amoxicillin and metronidazole. J Periodontol 2009,80:7254-1264.80812541264Sao Paulo State, Sao Paulo, SP, Brazil [04/13256-4]Sao Paulo State, Sao Paulo, SP, Brazil [04/13256-4

Theranostic applications of phage display to control leishmaniasis: selection of biomarkers for serodiagnostics, vaccination, and immunotherapy

AbstractPhage display is a high-throughput subtractive proteomic technology used for the generation and screening of large peptide and antibody libraries. It is based on the selection of phage-fused surface-exposed peptides that recognize specific ligands and demonstrate desired functionality for diagnostic and therapeutic purposes. Phage display has provided unmatched tools for controlling viral, bacterial, fungal, and parasitic infections, and allowed identification of new therapeutic targets to treat cancer, metabolic diseases, and other chronic conditions. This review presents recent advancements in serodiagnostics and prevention of leishmaniasis -an important tropical parasitic disease- achieved using phage display for the identification of novel antigens with improved sensitivity and specificity. Our focus is on theranostics of visceral leishmaniasis with the aim to develop biomarker candidates exhibiting both diagnostic and therapeutic potential to fight this important, yet neglected, tropical disease