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1.
Int J Pharm ; 466(1-2): 375-81, 2014 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-24657288

RESUMO

Inoculation of inbred mice by Leishmania major results in two different patterns. C57BL/6 mice display resistance against L. major but BALB/c mice show susceptibility to L. major with visceral infection, anemia and death. In this study, the effects of treatment of L. major-infected BALB/c mice with a ferroportin (Fpn)-encoding construct via nanoparticles were evaluated. A fragment encoding Fpn, a major regulator of iron homeostasis, was amplified and sub-cloned to a GFP expression vector to express Fpn-EGFP protein. This construct was incorporated in nanoparticles of alginate/chitosan polymers and orally administered to L. major-infected BALB/c mice. Blood hematocrit and iron, footpad size, parasite load and concentration of IFNG, IL4 and IL10 by ELISA were measured in the treated and untreated mice. The results indicated that the treated mice had significantly higher hematocrit and iron levels while exhibited significantly lower footpad size and parasite load measurements. Moreover, lower levels of IL4 and IL10 and higher ratios of IFNG/IL4 or IFNG/IL10 were shown in the treated, compared to the untreated mice. In conclusion, treating BALB/c mice infected with L. major with encapsulated Fpn-encoding construct in alginate/chitosan nanoparticles were shown to reduce the infection and improve anemia and immunity in the animal model of leishmaniasis.


Assuntos
Proteínas de Transporte de Cátions/administração & dosagem , Leishmaniose/tratamento farmacológico , Nanopartículas/administração & dosagem , Alginatos/química , Anemia/sangue , Anemia/tratamento farmacológico , Anemia/imunologia , Anemia/parasitologia , Animais , Proteínas de Transporte de Cátions/química , Quitosana/química , Citocinas/imunologia , Feminino , Ácido Glucurônico/química , Hematócrito , Ácidos Hexurônicos/química , Ferro/sangue , Leishmania major , Leishmaniose/sangue , Leishmaniose/imunologia , Leishmaniose/parasitologia , Linfonodos/imunologia , Linfonodos/parasitologia , Camundongos Endogâmicos BALB C , Nanopartículas/química , Carga Parasitária
2.
Vaccine ; 31(36): 3695-701, 2013 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-23770333

RESUMO

We have recently demonstrated that an attenuated strain of Salmonella enterica serovar Typhimurium unable to synthesize the zinc transporter ZnuABC (S. Typhimurium ΔznuABC), is able to protect mice against systemic and enteric salmonellosis and is safe in pigs. Here, we have tested the protective effects of S. Typhimurium ΔznuABC in pigs. Resistance to challenge with the fully virulent strain S. Typhimurium ATCC 14028 was assessed in animals vaccinated with S. Typhimurium ΔznuABC (two dosages tested), in controls vaccinated with a formalin-inactivated virulent strain and in unvaccinated controls. Clinical signs of salmonellosis, faecal shedding and bacterial colonization of organs were used to assess vaccine-induced protection. After the challenge, pigs vaccinated with the attenuated S. Typhimurium ΔznuABC strain did not display clinical signs of salmonellosis (fever or diarrhoea). The vaccine also reduced intestinal tract colonization and faecal shedding of the fully virulent Salmonella strain, as compared to control groups. S. Typhimurium ΔznuABC represents a promising candidate vaccine against salmonellosis in pigs.


Assuntos
Proteínas de Bactérias/imunologia , Proteínas de Transporte de Cátions/imunologia , Salmonelose Animal/prevenção & controle , Vacinas contra Salmonella/imunologia , Administração Oral , Animais , Proteínas de Bactérias/administração & dosagem , Derrame de Bactérias , Proteínas de Transporte de Cátions/administração & dosagem , Fezes/microbiologia , Feminino , Imunidade nas Mucosas , Interferon gama/imunologia , Mucosa Bucal/imunologia , Vacinas contra Salmonella/administração & dosagem , Salmonella typhimurium/imunologia , Salmonella typhimurium/patogenicidade , Sus scrofa , Fator de Necrose Tumoral alfa/imunologia , Vacinas Atenuadas/administração & dosagem , Vacinas Atenuadas/imunologia , Virulência
3.
Proc Natl Acad Sci U S A ; 103(45): 16942-7, 2006 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-17075065

RESUMO

Staphylococcus aureus is the most common cause of hospital-acquired infection. Because of the emergence of antibiotic-resistant strains, these infections represent a serious public health threat. To develop a broadly protective vaccine, we tested cell wall-anchored surface proteins of S. aureus as antigens in a murine model of abscess formation. Immunization with four antigens (IsdA, IsdB, SdrD, and SdrE) generated significant protective immunity that correlated with the induction of opsonophagocytic antibodies. When assembled into a combined vaccine, the four surface proteins afforded high levels of protection against invasive disease or lethal challenge with human clinical S. aureus isolates.


Assuntos
Vacinas Bacterianas/administração & dosagem , Staphylococcus aureus/imunologia , Abscesso/prevenção & controle , Animais , Antígenos de Bactérias/administração & dosagem , Antígenos de Bactérias/genética , Antígenos de Bactérias/imunologia , Antígenos de Superfície/administração & dosagem , Antígenos de Superfície/genética , Proteínas de Bactérias/administração & dosagem , Proteínas de Bactérias/genética , Proteínas de Bactérias/imunologia , Vacinas Bacterianas/genética , Proteínas de Ligação ao Cálcio/administração & dosagem , Proteínas de Ligação ao Cálcio/genética , Proteínas de Ligação ao Cálcio/imunologia , Proteínas de Transporte de Cátions/administração & dosagem , Proteínas de Transporte de Cátions/genética , Proteínas de Transporte de Cátions/imunologia , Feminino , Humanos , Proteínas de Membrana/administração & dosagem , Proteínas de Membrana/genética , Proteínas de Membrana/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Infecções Estafilocócicas/imunologia , Infecções Estafilocócicas/prevenção & controle , Staphylococcus aureus/genética , Staphylococcus aureus/patogenicidade , Vacinas Combinadas/administração & dosagem , Vacinas Combinadas/genética
4.
Infect Immun ; 74(4): 2215-23, 2006 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-16552052

RESUMO

Staphylococcus aureus is a major cause of nosocomial infections worldwide, and the rate of resistance to clinically relevant antibiotics, such as methicillin, is increasing; furthermore, there has been an increase in the number of methicillin-resistant S. aureus community-acquired infections. Effective treatment and prevention strategies are urgently needed. We investigated the potential of the S. aureus surface protein iron surface determinant B (IsdB) as a prophylactic vaccine against S. aureus infection. IsdB is an iron-sequestering protein that is conserved in diverse S. aureus clinical isolates, both methicillin resistant and methicillin sensitive, and it is expressed on the surface of all isolates tested. The vaccine was highly immunogenic in mice when it was formulated with amorphous aluminum hydroxyphosphate sulfate adjuvant, and the resulting antibody responses were associated with reproducible and significant protection in animal models of infection. The specificity of the protective immune responses in mice was demonstrated by using an S. aureus strain deficient for IsdB and HarA, a protein with a high level of identity to IsdB. We also demonstrated that IsdB is highly immunogenic in rhesus macaques, inducing a more-than-fivefold increase in antibody titers after a single immunization. Based on the data presented here, IsdB has excellent prospects for use as a vaccine against S. aureus disease in humans.


Assuntos
Anticorpos Antibacterianos/biossíntese , Antígenos de Bactérias/imunologia , Proteínas de Transporte de Cátions/imunologia , Macaca mulatta/imunologia , Sepse/imunologia , Infecções Estafilocócicas/imunologia , Vacinas Antiestafilocócicas/imunologia , Staphylococcus aureus/imunologia , Animais , Anticorpos Antibacterianos/sangue , Antígenos de Bactérias/administração & dosagem , Antígenos de Bactérias/química , Proteínas de Transporte de Cátions/administração & dosagem , Proteínas de Transporte de Cátions/química , Modelos Animais de Doenças , Feminino , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos ICR , Sepse/mortalidade , Sepse/prevenção & controle , Homologia de Sequência de Aminoácidos , Infecções Estafilocócicas/mortalidade , Infecções Estafilocócicas/prevenção & controle , Vacinas Antiestafilocócicas/administração & dosagem , Staphylococcus aureus/isolamento & purificação , Taxa de Sobrevida
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