Leishmaniases are infectious-parasitic diseases that impact public health around the world. Antileishmanial drugs presented toxicity and increase in parasitic resistance. Studies with natural products show an alternative to this effect, and several metabolites have demonstrated potential in the treatment of various diseases. Terminalia catappa is a plant species with promising pharmaceutical properties. The objective of this work was to evaluate the therapeutic potential of extracts and fractions of T. catappa on Leishmania amazonensis and investigate the immunomodulatory mechanisms associated with its action. In anti-Leishmania assays, the ethyl acetate fraction exhibited activity against promastigotes (IC50 86.07 ± 1.09 μg/mL) and low cytotoxicity (CC50 517.70 ± 1.68 μg/mL). The ethyl acetate fraction also inhibited the intracellular parasite (IC50 25.74 ± 1.08 μg/mL) with a selectivity index of 20.11. Treatment with T. catappa ethyl acetate fraction did not alter nitrite production by peritoneal macrophages stimulated with L. amazonensis, although there was a decrease in unstimulated macrophages treated at 50 μg/mL (p = 0.0048). The T. catappa ethyl acetate fraction at 100 μg/mL increased TNF-α levels (p = 0.0238) and downregulated HO-1 (p = 0.0030) and ferritin (p = 0.0002) gene expression in L. amazonensis-stimulated macrophages. Additionally, the total flavonoid and ellagic acid content for ethyl acetate fraction was 13.41 ± 1.86 mg QE/g and 79.25 mg/g, respectively. In conclusion, the T. catappa ethyl acetate fraction showed leishmanicidal activity against different forms of L. amazonensis and displayed immunomodulatory mechanisms, including TNF-α production and expression of pro and antioxidant genes.
Dogs with visceral leishmaniasis play a key role in the transmission cycle of Leishmania infantum to humans in the urban environment. There is a consensus regarding the importance of developing a vaccine to control this disease. Despite many efforts to develop a protective vaccine against CVL, the ones currently available, Leish-tec® and LetiFend®, have limited effectiveness. This is due, in part, to the complexity of the immune response of the naturally infected dogs against the parasite and the complexity of the parasite transmission cycle. Thus, strategies, such as the development of a transmission-blocking vaccines (TBVs) already being applied to other vector-borne diseases like malaria and dengue, would be an attractive alternative to control leishmaniasis. TBVs induce the production of antibodies in the vertebrate host, which can inhibit parasite development in the vector and/or interfere with aspects of vector biology, leading to an interruption of parasite transmission. To date, there are few TBV studies for CVL and other leishmaniasis forms. However, the few studies that exist show promising results, thus justifying the further development of this approach.
Malaria is a parasitic infection that is a great public health concern and is responsible for high mortality rates worldwide. Different strategies have been employed to improve disease control, demonstrating the ineffectiveness of controlling vectors, and parasite resistance to antimalarial drugs requires the development of an effective preventive vaccine. There are countless challenges to the development of such a vaccine directly related to the parasite’s complex life cycle. After more than four decades of basic research and clinical trials, the World Health Organization (WHO) has recommended the pre-erythrocytic Plasmodium falciparum (RTS, S) malaria vaccine for widespread use among children living in malaria-endemic areas. However, there is a consensus that major improvements are needed to develop a vaccine with a greater epidemiological impact in endemic areas. This review discusses novel strategies for malaria vaccine design taking the target stages within the parasite cycle into account. The design of the multi-component vaccine shows considerable potential, especially as it involves transmission-blocking vaccines (TBVs) that eliminate the parasite’s replication towards sporozoite stage parasites during a blood meal of female anopheline mosquitoes. Significant improvements have been made but additional efforts to achieve an efficient vaccine are required to improve control measures. Different strategies have been employed, thus demonstrating the ineffectiveness in controlling vectors, and parasite resistance to antimalarial drugs requires the development of a preventive vaccine. Despite having a vaccine in an advanced stage of development, such as the RTS, S malaria vaccine, the search for an effective vaccine against malaria is far from over. This review discusses novel strategies for malaria vaccine design taking into account the target stages within the parasite’s life cycle.
Background/Objectives: Amblyomma sculptum is among the most dangerous ticks in South America, as it is the species most associated with humans and is the main vector of Rickettsia rickettsii. In the face of the problems related to tick control based on chemical acaricides, vaccines emerge as a promising method. In previous works, three salivary recombinant proteins (rAs8.9kDa, rAsKunitz, and rAsBasicTail) and one protein based on intestinal immunogenic regions (rAsChimera) were described with 59 to 92% vaccine efficacy against A. sculptum females. Here, we evaluate novel vaccine formulations containing binary or multiple combinations of the antigens rAs8.9kDa, rAsKunitz, rAsBasicTail, and rAsChimera against the three instars of the tick. Methods: A control group of mice was immunized with adjuvant alone (aluminum hydroxide gel) and compared to five groups immunized with formulations containing two, three, or four of the antigens. Results: The formulations were safe, with no significant alterations to host behavior and hematological or biochemical parameters. Immunizations induced a significant increase in the CD19+ B lymphocyte percentage in all groups, but no difference was seen for CD8+ and CD4+ T lymphocytes or CD14+ monocytes. The best protection was observed for the formulations containing two antigens, which reached above 98% efficacy, while the groups containing three or four antigens presented 92.7 and 94.4% efficacy, respectively. Conclusions: All antigen combinations were promising as vaccine formulations against A. sculptum. The formulation containing rAs8.9kDa and rAsChimera showed the best efficacy and should be focused on in further experiments.
Malaria is a parasitic infection that is a great public health concern and is responsible for high mortality rates worldwide. Different strategies have been employed to improve disease control, demonstrating the ineffectiveness of controlling vectors, and parasite resistance to antimalarial drugs requires the development of an effective preventive vaccine. There are countless challenges to the development of such a vaccine directly related to the parasite's complex life cycle. After more than four decades of basic research and clinical trials, the World Health Organization (WHO) has recommended the pre-erythrocytic Plasmodium falciparum (RTS, S) malaria vaccine for widespread use among children living in malaria-endemic areas. However, there is a consensus that major improvements are needed to develop a vaccine with a greater epidemiological impact in endemic areas. This review discusses novel strategies for malaria vaccine design taking the target stages within the parasite cycle into account. The design of the multi-component vaccine shows considerable potential, especially as it involves transmission-blocking vaccines (TBVs) that eliminate the parasite's replication towards sporozoite stage parasites during a blood meal of female anopheline mosquitoes. Significant improvements have been made but additional efforts to achieve an efficient vaccine are required to improve control measures. Different strategies have been employed, thus demonstrating the ineffectiveness in controlling vectors, and parasite resistance to antimalarial drugs requires the development of a preventive vaccine. Despite having a vaccine in an advanced stage of development, such as the RTS, S malaria vaccine, the search for an effective vaccine against malaria is far from over. This review discusses novel strategies for malaria vaccine design taking into account the target stages within the parasite’s life cycle.