Variation in the immune response to adenoviral vectors in the brain: influence of mouse strain, environmental conditions and priming

Abstract

E1-deleted adenoviral vectors expressing the bacterial ␤-ently made higher antibody responses than C57BL/6J galactosidase gene were inoculated into the brain of mice. Although adenoviral vectors induced an inflammatory unprimed and primed C3H.He or C57BL/6J mice housed response under all conditions, mice housed in SPF faciliunder either conventional or specific-pathogen-free (SPF) ties exhibited less inflammation than conventional mice conditions. The kinetics of immune responses to both the and transgene expression persisted for longer. Irrespective vector and the transgene were investigated. In mice preof whether the mice had been deliberately primed to adenviously sensitized to adenovirus, the leukocyte infiltrate in ovirus, antibody titres were consistently lower in SPF mice the brain was dominated by CD8 + T cells, whereas in compared with conventional mice. This study clearly demunprimed mice CD4 + T cells were present at higher levels.onstrates that environmental conditions, as well as preAs expected, antibody titres to both adenovirus and ␤-vious priming to adenovirus, will affect both the quality and galactosidase were higher in primed mice than in unprimed duration of the immune response triggered by gene mice after intracranial inoculation. C3H.He mice consistdelivery to the brain.

Reversible Demyelination, Blood-Brain Barrier Breakdown, and Pronounced Neutrophil Recruitment Induced by Chronic IL-1 Expression in the Brain

“…This is likely due to the low pfu that we used for this study and to the use of finely polished capillaries for the infusion that minimize the trauma associated with the surgery. 31 Under our conditions, we achieved long transgene expression (for 30 days) with no chronic inflammatory response due to the vector itself.…”

Bcl-2 expression by retrograde transport of adenoviral vectors with Cre-loxP recombination system in motor neurons of mutant SOD1 transgenic mice

“…22 In addition to restricting transgene expression to motor neurons, maintaining long-term expression is one of the major goals for gene therapy in the motor neuron diseases. Transgene expression using adenoviral vectors is transient in most in vivo systems because of cellular and humoral immune responses triggered following the administration of adenoviral vectors, 15,16 although the brain is traditionally considered an immunologically privileged organ. Most studies on the route of delivery of vectors have utilized local intracerebral or intraventricularly stereotactic injections of vectors, which have limited clinical applicability.…”

“…11 Adenoviral vectors have several attractive properties as vehicles of gene transfer into CNS, [12][13][14] although it has become apparent that adenoviral vectors are immunogenic and can induce cytopathic effects. 15,16 They can be prepared in high titer, can be used safely for human vaccination, and can accommodate relatively large gene inserts; they are particularly useful for infection and expression in terminally differentiated non-dividing cells, such as neurons. With regard to the specificity of gene transfer to CNS, the selective targeting of transgene expression to particular cells is required.…”

The dl1520 Virus Is Found Preferentially in Tumor Tissue after Direct Intratumoral Injection in Oral Carcinoma

“…We did not detect any evidence that these differences significantly affected the dl1520 virus in this study, but it could be that the differences in viral detection were due to viral movement out of normal tissue as well as replication within tissue. It is known that inflammatory cells respond to gene therapy adenoviral vectors in both normal and tumor tissues (23,24). There is no evidence that this effect is stronger in reducing viral levels in normal, as opposed to tumor, tissue either in this study or from previous studies.…”