title: Combined immunization using DNA-Sm14 and DNA-Hsp65 increases CD8+ memory T cells, reduces chronic pathology and decreases egg viability during Schistosoma mansoni infection.
abstract: BACKGROUND
  Schistosomiasis is one of the most important neglected diseases found in developing countries and affects 249 million people worldwide. The development of an efficient vaccination strategy is essential for the control of this disease. Previous work showed partial protection induced by DNA-Sm14 against Schistosoma mansoni infection, whereas DNA-Hsp65 showed immunostimulatory properties against infectious diseases, autoimmune diseases, cancer and antifibrotic properties in an egg-induced granuloma model.
  
  
  METHODS
  C57BL/6 mice received 4 doses of DNA-Sm14 (100 μg/dose) and DNA-Hsp65 (100 μg/dose), simultaneously administrated, or DNA-Sm14 alone, once a week, during four weeks. Three groups were included: 1- Control (no immunization); 2- DNA-Sm14; 3- DNA-Sm14/DNA-Hsp65. Two weeks following last immunization, animals were challenged subcutaneously with 30 cercariae. Fifteen, 48 and 69 days after infection splenocytes were collected to evaluate the number of CD8+ memory T cells (CD44(high)CD62(low)) using flow cytometry. Forty-eight days after challenge adult worms were collected by portal veins perfusion and intestines were collected to analyze the intestinal egg viability. Histological, immunohistochemical and soluble quantification of collagen and α-SMA accumulation were performed on the liver.
  
  
  RESULTS
  In the current work, we tested a new vaccination strategy using DNA-Sm14 with DNA-Hsp65 to potentiate the protection against schistosomiasis. Combined vaccination increased the number of CD8+ memory T cells and decreased egg viability on the intestinal wall of infected mice. In addition, simultaneous vaccination with DNA-Sm14/DNA-Hsp65 reduced collagen and α-SMA accumulation during the chronic phase of granuloma formation.
  
  
  CONCLUSIONS
  Simultaneous vaccination with DNA-Sm14/DNA-Hsp65 showed an immunostimulatory potential and antifibrotic property that is associated with the reduction of tissue damage on Schistosoma mansoni experimental infection.
authors.forename: Milena Sobral
authors.initials: MS
authors.lastname: Espíndola
authors.forename: Fabiani Gai
authors.initials: FG
authors.lastname: Frantz
authors.forename: Luana Silva
authors.initials: LS
authors.lastname: Soares
authors.forename: Ana Paula
authors.initials: AP
authors.lastname: Masson
authors.forename: Cristiane
authors.initials: C
authors.lastname: Tefé-Silva
authors.forename: Claudia Silva
authors.initials: CS
authors.lastname: Bitencourt
authors.forename: Sérgio Costa
authors.initials: SC
authors.lastname: Oliveira
authors.forename: Vanderlei
authors.initials: V
authors.lastname: Rodrigues
authors.forename: Simone Gusmão
authors.initials: SG
authors.lastname: Ramos
authors.forename: Célio Lopes
authors.initials: CL
authors.lastname: Silva
authors.affiliation: Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Av, do Café s/n 14040-903 Ribeirão Preto, São Paulo, Brazil. faccioli@fcfrp.usp.br.
authors.forename: Lúcia Helena
authors.initials: LH
authors.lastname: Faccioli
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes; D018834:Chaperonin 60 / Q000276:immunology*; D003906:Developing Countries; D050612:Fatty Acid Transport Proteins / Q000276:immunology*; D015801:Helminth Proteins / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D012550:Schistosoma mansoni / Q000276:immunology*; D012555:Schistosomiasis mansoni / Q000276:immunology / Q000517:prevention & control*; D014611:Vaccination / Q000379:methods*
chemical_list: D001426:Bacterial Proteins; D018834:Chaperonin 60; D050612:Fatty Acid Transport Proteins; D015801:Helminth Proteins; C074119:heat-shock protein 65, Mycobacterium; C068709:SM14 protein, Schistosoma mansoni