Safety and Immunogenicity of an In Vivo Muscle Electroporation Delivery System for DNA-hsp65 Tuberculosis Vaccine in Cynomolgus Monkeys

A Bacille Calmette–Guérin (BCG) is still the only licensed vaccine for the prevention of tuberculosis, providing limited protection against Mycobacterium tuberculosis infection in adulthood. New advances in the delivery of DNA vaccines by electroporation have been made in the past decade. We evaluated the safety and immunogenicity of the DNA-hsp65 vaccine administered by intramuscular electroporation (EP) in cynomolgus macaques. Animals received three doses of DNA-hsp65 at 30-day intervals. We demonstrated that intramuscular electroporated DNA-hsp65 vaccine immunization of cynomolgus macaques was safe, and there were no vaccine-related effects on hematological, renal, or hepatic profiles, compared to the pre-vaccination parameters. No tuberculin skin test conversion nor lung X-ray alteration was identified. Further, low and transient peripheral cellular immune response and cytokine expression were observed, primarily after the third dose of the DNA-hsp65 vaccine. Electroporated DNA-hsp65 vaccination is safe but provides limited enhancement of peripheral cellular immune responses. Preclinical vaccine trials with DNA-hsp65 delivered via EP may include a combination of plasmid cytokine adjuvant and/or protein prime–boost regimen, to help the induction of a stronger cellular immune response

No association of IFNG+874T/A SNP and NOS2A-954G/C SNP variants with nitric oxide radical serum levels or susceptibility to tuberculosis in a Brazilian population subset

Submitted by Repositório Arca ([email protected]) on 2019-04-24T17:15:36Z No. of bitstreams: 1 license.txt: 1748 bytes, checksum: 8a4605be74aa9ea9d79846c1fba20a33 (MD5)Approved for entry into archive by Janaína Nascimento ([email protected]) on 2019-09-27T14:41:49Z (GMT) No. of bitstreams: 2 ve_Leandro_Ana_etal_INI_2013.pdf: 613537 bytes, checksum: 2da9ad57c3a06a3e5d8a98f3a6e52fba (MD5) license.txt: 1748 bytes, checksum: 8a4605be74aa9ea9d79846c1fba20a33 (MD5)Made available in DSpace on 2019-09-27T14:41:49Z (GMT). No. of bitstreams: 2 ve_Leandro_Ana_etal_INI_2013.pdf: 613537 bytes, checksum: 2da9ad57c3a06a3e5d8a98f3a6e52fba (MD5) license.txt: 1748 bytes, checksum: 8a4605be74aa9ea9d79846c1fba20a33 (MD5) Previous issue date: 2013Fundação Oswaldo Cruz. Instituto de Pesquisa Clínica Evandro Chagas. Laboratório de Imunologia e Imunogenética em Doenças Infecciosas. Rio de Janeiro, RJ, Brasil / Texas Biomedical Research Institute. Department of Genetics and Southwest National Primate Research Center. San Antonio, TX, USA.Fundação Oswaldo Cruz. Instituto de Pesquisa Clínica Evandro Chagas. Laboratório de Imunologia e Imunogenética em Doenças Infecciosas. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto de Pesquisa Clínica Evandro Chagas. Laboratório de Imunologia e Imunogenética em Doenças Infecciosas. Rio de Janeiro, RJ, Brasil.Texas Biomedical Research Institute. Department of Genetics and Southwest National Primate Research Center. San Antonio, TX, USA.Fundação Oswaldo Cruz. Instituto de Pesquisa Clínica Evandro Chagas. Laboratório de Imunologia e Imunogenética em Doenças Infecciosas. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto de Pesquisa Clínica Evandro Chagas. Laboratório de Imunologia e Imunogenética em Doenças Infecciosas. Rio de Janeiro, RJ, Brasil.Tuberculosis (TB) is one of the most common infectious diseases in the world. Mycobacterium tuberculosis infection leads to pulmonary active disease in approximately 5–10% of exposed individuals. Both bacteria- and host-related characteristics influence latent infection and disease. Host genetic predisposition to develop TB may involve multiple genes and their polymorphisms. It was reported previously that interferon gamma (IFN-) and nitric oxide synthase 2 (NOS2) are expressed on alveolar macrophages from TB patients and are responsible for bacilli control; thus, we aimed this study at genotyping single nucleotide polymorphisms IFNG+874T/A SNP and NOS2A-954G/C SNP to estimate their role on TB susceptibility and determine whether these polymorphisms influence serum nitrite and NO− production. This case-control study enrolled 172 TB patients and 179 Thealthy controls. Neither polymorphism was associated with susceptibility to TB. NOS2A-954G/C SNP was not associated with serum levels of nitrite and NO−. These results indicate that variants of IFNG+874T/A SNP and NOS2A-954G/C SNP do not influence TB susceptibility or the secretion of nitric oxide radicals in the study population

A protocol update for the Selenium Treatment and Chagasic Cardiomyopathy (STCC) trial

Abstract Several studies evaluating clinical forms of chronic Chagas disease show that about one-third of patients present cardiac involvement. Heart failure, sudden death and cardioembolic stroke are the main mechanisms of death in Chagas heart disease. The impact of specific etiologic treatment on the prognosis of patients with chronic Chagas heart disease is very limited regardless of the presence or absence of heart failure. Patients with symptomatic Chagas heart disease present serum selenium (Se) levels lower than patients without Chagas heart disease. Moreover, Se supplementation in animal models showed promising results. The aim of this trial is to estimate the effect of Se treatment on prevention of heart disease progression in patients with Chagas cardiomyopathy. However, we had to introduce some protocol modifications in order to keep trial feasibility, as follows: the primary outcome was restricted to left ventricular ejection fraction as a continuous variable, excluding disease progression; the follow-up period was decreased from 5 years to 1 year, an adjustment that might increase the participation rate of our study; the superior age limit was increased from 65 to 75 years; and diabetes mellitus was no longer considered an exclusion criterion. All of these protocol modifications were extensively debated by the research team enrolled in the design, recruitment and conduction of the clinical trial to guarantee a high scientific quality. Trial registration Clinical Trials.gov, NCT00875173. Registered on 20 October 2008