RESUMO
Influenza and Respiratory Syncytial virus (RSV) infections together contribute significantly to the burden of acute lower respiratory tract infections. Despite the disease burden, no approved RSV vaccine is available. While approved vaccines are available for influenza, seasonal vaccination is required to maintain protection. In addition to both being respiratory viruses, they follow a common seasonality, which warrants the necessity for a concerted vaccination approach. Here, we designed bivalent vaccines by utilizing highly conserved sequences, targeting both influenza A and RSV, as either a chimeric antigen or individual antigens separated by a ribosome skipping sequence. These vaccines were found to be effective in protecting the animals from challenge by either virus, with mechanisms of protection being substantially interrogated in this communication.
Assuntos
Vacinas contra Influenza , Influenza Humana , Infecções por Vírus Respiratório Sincicial , Camundongos , Animais , Humanos , Vírus Sinciciais Respiratórios/genética , Vacinas Combinadas , Anticorpos Antivirais , Infecções por Vírus Respiratório Sincicial/prevenção & controle , Vacinas contra Influenza/genética , Anticorpos NeutralizantesRESUMO
Introduction: The incidence of Lyme disease (LD) in Canada and the United States has risen over the last decade, nearing 480,000 cases each year. Borrelia burgdorferi sensu lato, the causative agent of LD, is transmitted to humans through the bite of an infected tick, resulting in flu-like symptoms and often a characteristic bull's-eye rash. In more severe cases, disseminated bacterial infection can cause arthritis, carditis and neurological impairments. Currently, no vaccine is available for the prevention of LD in humans. Methods: In this study, we developed a lipid nanoparticle (LNP)-encapsulated DNA vaccine encoding outer surface protein C type A (OspC-type A) of B. burgdorferi. Results: Vaccination of C3H/HeN mice with two doses of the candidate vaccine induced significant OspC-type A-specific antibody titres and borreliacidal activity. Analysis of the bacterial burden following needle challenge with B. burgdorferi (OspC-type A) revealed that the candidate vaccine afforded effective protection against homologous infection across a range of susceptible tissues. Notably, vaccinated mice were protected against carditis and lymphadenopathy associated with Lyme borreliosis. Discussion: Overall, the results of this study provide support for the use of a DNA-LNP platform for the development of LD vaccines.
Assuntos
Borrelia burgdorferi , Doença de Lyme , Miocardite , Vacinas de DNA , Humanos , Camundongos , Animais , Vacinas Bacterianas , Camundongos Endogâmicos C3H , DNARESUMO
Much evidence indicates that schizophrenic patients exhibit deficits on tests of executive functioning. It is therefore hypothesized that individuals with high schizotypal personality traits that may have a predisposition to schizophrenia, are also likely to exhibit impairments in neuropsychological tests of executive function. The sample consisted of 65 healthy controls that were divided into high and low scorers on the Schizotypal Personality Questionnaire (SPQ-B: Raine et al., 1995). Participants completed a battery of executive tasks (category and letter fluency, the Hayling test, Zoo map); however, a MANOVA revealed no significant differences between high and low SPQ scorers. Nevertheless, high SPQ scorers scored significantly higher on the Dysexecutive Questionnaire (DEX) self-rating scale of everyday executive problems; and these self-ratings correlated significantly with the disorganisation and cognitive-perceptual features of the SPQ-B, but not with the interpersonal features. This suggests that perceived executive dysfunction is pre-morbidly present and may become evident in test performance only with the onset of schizophrenia itself.