Investigating Immunization With Nucleotide Enzymes of Schistosoma mansoni: Nucleoside Diphosphate Kinase and Adenylosuccinate Lyase as New Antigenic Targets Against Schistosomiasis.

Túlio Di Orlando Cagnazzo,Tiago Manuel Fernandes Mendes,Silmara Marques Allegretti,Ana Carolina Maragno Fattori,Camila Tita Nogueira,Fernanda De Freitas Anibal,Edson Garcia Soares,Larissa Romanello,Débora Meira Neris,Cynthia Aparecida De Castro,Humberto D’Muniz Pereira,Bruna Dias De Lima Fragelli,Ricardo De Oliveira Correia,Juliana Roberta Torini,Yulli Roxenne Albuquerque

doi:10.3389/fimmu.2020.569988

Abstract

Schistosomiasis, caused by Schistosoma mansoni trematode worm, affects more than 1.5 million people in Brazil. The current treatment consists in the administration of Praziquantel, the only medicine used for treatment for more than 40 years. Some of the limitations of this drug consist in its inactivity against schistosomula and parasite eggs, the appearance of resistant strains and non-prevention against reinfection. Thus, the objective of this study was to evaluate the effect of immunization with recombinant functional enzymes of the purine salvage pathway of S. mansoni, Nucleoside Diphosphate Kinase (NDPK) and Adenylosuccinate Lyase (ADSL), to evaluate the host immune response, as well as the parasite load after vaccination. For this, Balb/c mice were divided into 5 groups: control (uninfected and untreated), non-immunized/infected, NDPK infected, ADSL infected, and NDPK + ADSL infected. Immunized groups received three enzyme dosages, with a 15-day interval between each dose, and after 15 days of the last application the animals were infected with 80 cercariae of S. mansoni. On the 47th day after the infection, fecal eggs were counted and, on the 48th day after the infection, the evaluation of leukocyte response, parasite load, antibody production, cytokines quantification, and histopathological analysis were performed. The results showed that immunizations with NDPK, ADSL or NDPK + ADSL promoted a discreet reduction in eosinophil counts in lavage of peritoneal cavity. All immunized animals showed increased production and secretion of IgG1, IgG2a, and IgE antibodies. Increased production of IL-4 was observed in the group immunized with the combination of both enzymes (NDPK + ADSL). In addition, in all immunized groups there were reductions in egg counts in the liver and intestine, such as reductions in liver granulomas. Thus, we suggest that immunizations with these enzymes could contribute to the reduction of schistosomiasis transmission, besides being important in immunopathogenesis control of the disease.

Highlights

According to the World Health Organization (WHO), a group of diseases called Neglected Tropical Diseases (NTD) affects approximately 1 billion people in regions with high rates of tropical and subtropical climate poverty, and costs developing countries’ economies billions of dollars every year [1]
The Infected group (INF) immunized with both recombinant enzymes (NDPK + ADSL), showed the highest values when compared to the other groups, in addition to the data of eggs/feces found in each animal being more dispersed in this group
In the peritoneal cavity lavage (PCL) (Figure 3B) there was a significant increase in the number of eosinophils in all groups when compared to the Control group (CTRL) group

Summary

Introduction

According to the World Health Organization (WHO), a group of diseases called Neglected Tropical Diseases (NTD) affects approximately 1 billion people in regions with high rates of tropical and subtropical climate poverty, and costs developing countries’ economies billions of dollars every year [1]. An important highlight within this group of diseases is schistosomiasis, which affects over 200 million people worldwide, with an estimated at-risk population of 700 million [2]. With approximately 1.5 million people living in areas of risk for contamination by the parasite [3], mansonic schistosomiasis represents great importance in socioeconomic terms and impact on public health in the country, since influences from the cognitive response of school-age children to the economic production of the country and its consequent development. The fact that the drug is not effective against schistosomula or eggs of S. mansoni makes its use restricted [5]. Another limiting factor for the indiscriminate use of the drug is the emergence of resistant strains over the years [6]. One of the most important aspects of drug failure is its use as a control method, since it does not prevent reinfection [5, 7, 8]

Objectives

Methods

Results

Conclusion