Reviews in medical virology
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Review Comparative Study
New generation smallpox vaccines: a review of preclinical and clinical data.
The recognition that smallpox is a potential threat agent of bioterrorism has engendered renewed interest in the development of improved vaccines against this pathogen. The purpose of this paper is to review current data regarding novel approaches to smallpox vaccines in comparison with traditional vaccine strategies. The method used is a literature search using overlapping search terms and citations from the relevant, published literature. ⋯ The incidence of other serious, albeit uncommon, adverse events of smallpox vaccines cannot be determined for newer vaccine approaches because these agents have not yet been deployed on a scale large enough to discern rare events. Since 2001, progress towards improved smallpox vaccines has been accelerated, spurred on by the threat of bioterrorism. Among newer vaccine candidates, replication-competent, highly attenuated vaccinia and tissue culture-derived live vaccinia appear to offer the greatest potential for efficacy, although it is unclear whether these products offer a safer alternative to existing first generation vaccines.
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Review
Immunopathology of RSV infection: prospects for developing vaccines without this complication.
Respiratory syncytial virus is the most important cause of lower respiratory tract infection in infants and young children. RSV clinical disease varies from rhinitis and otitis media to bronchiolitis and pneumonia. An increased incidence of asthma later in life has been associated with the more severe lower respiratory tract infections. ⋯ Subunit vaccines formulated with appropriate adjuvants may be adequate for previously exposed individuals. However, intranasally delivered genetically engineered attenuated or vectored vaccines are currently most promising for newborns, as they are expected to induce a balanced immune response similar to that elicited to natural infection and not be subject to interference from maternal antibodies. Maternal vaccination may be the optimal strategy to protect the very young infants.
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Since its introduction to North America in 1999, West Nile virus, an arthropod-borne flavivirus, has become the most significant cause of epidemic encephalitis in the western hemisphere. While most human infections with the virus are asymptomatic and the majority of symptomatic persons experience febrile illness, severe neurologic manifestations, including meningitis, encephalitis, and poliomyelitis may be seen. This review summarizes the virology, epidemiology and pathogenesis of human infection with West Nile virus, and details recent advances in our understanding of the pathophysiology and various clinical manifestations of infection.
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High-grade gliomas constitute an important challenge to modern medicine, and although great effort has been made to prolong patient survival, the prognosis for this disease remains poor. Due to recent discoveries in the molecular basis of gliomas, gene therapy is becoming a promising alternative. ⋯ Such vectors, when rendered conditionally replicative via transductional and transcriptional modifications, offer great promise for patients with malignant brain tumours. We review data from preclinical and clinical studies utilising such vectors and discuss the limitations and future perspectives of CRAd oncolytic therapy for malignant glioma.
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The hypothesis that human endogenous retroviruses (HERVs) play a role in autoimmune diseases is subject to increasing attention. HERVs represent both putative susceptibility genes and putative pathogenic viruses in the immune-mediated neurological disease multiple sclerosis (MS). Gammaretroviral HERV sequences are found in reverse transcriptase-positive virions produced by cultured mononuclear cells from MS patients, and they have been isolated from MS samples of plasma, serum and CSF, and characterised to some extent at the nucleotide, protein/enzyme, virion and immunogenic level. ⋯ The activating factor(s) in the process resulting in protein or virion production may be members of the Herpesviridae. Several herpes viruses, such as HSV-1, VZV, EBV and HHV-6, have been associated with MS pathogenesis, and retroviruses and herpes viruses have complex interactions. The current understanding of HERVs, and specifically the investigations of HERV activation and expression in MS are the major subjects of this review, which also proposes to synergise the herpes and HERV findings, and presents several possible pathogenic mechanisms for HERVs in MS.