scholarly journals Augmentation of transgene-encoded protein after neonatal injection of adeno-associated virus improves hepatic copy number without immune responses

2015 ◽  
Vol 78 (3) ◽  
pp. 239-246 ◽  
Author(s):  
Denise S. Tai ◽  
Chuhong Hu ◽  
Elizabeth H. Kim ◽  
Gerald S. Lipshutz
Keyword(s):  
Immune Responses ◽  
Copy Number ◽  
Adeno Associated Virus ◽  
Neonatal Injection

scholarly journals Human Immune Responses to Adeno-Associated Virus (AAV) Vectors

2020 ◽  
Vol 11 ◽  
Author(s):  
Giuseppe Ronzitti ◽  
David-Alexandre Gross ◽  
Federico Mingozzi
Keyword(s):  
Immune Responses ◽  
Adeno Associated Virus ◽  
Human Immune

scholarly journals Humoral and Cellular Capsid-Specific Immune Responses to Adeno-Associated Virus Type 1 in Randomized Healthy Donors

2012 ◽  
Vol 188 (12) ◽  
pp. 6418-6424 ◽  
Author(s):  
Philippe Veron ◽  
Christian Leborgne ◽  
Virginie Monteilhet ◽  
Sylvie Boutin ◽  
Samia Martin ◽  
...  
Keyword(s):  
Immune Responses ◽  
Virus Type ◽  
Adeno Associated Virus ◽  
Healthy Donors

scholarly journals T Cell-Mediated Immune Responses to AAV and AAV Vectors

2021 ◽  
Vol 12 ◽  
Author(s):  
Hildegund C. J. Ertl
Keyword(s):  
T Cell ◽  
Gene Transfer ◽  
Immune Responses ◽  
De Novo ◽  
T Cell Responses ◽  
Adeno Associated Virus ◽  
Effector Functions ◽  
Cell Responses ◽  
High Doses

Adeno-associated virus (AAV)-mediated gene transfer has benefited patients with inherited diseases, such as hemophilia B, by achieving long-term expression of the therapeutic transgene. Nevertheless, challenges remain due to rejection of AAV-transduced cells, which in some, but not all, patients can be prevented by immunosuppression. It is assumed that CD8+ T cells induced by natural infections with AAVs are recalled by the AAV vector’s capsid and upon activation eliminate cells expressing the degraded capsid antigens. Alternatively, it is feasible that AAV vectors, especially if given at high doses, induce de novo capsid- or transgene product-specific T cell responses. This chapter discusses CD8+ T cell responses to AAV infections and AAV gene transfer and avenues to prevent their activation or block their effector functions.

scholarly journals Liver-Directed AAV8 Booster Vaccine Expressing Plasmodium falciparum Antigen Following Adenovirus Vaccine Priming Elicits Sterile Protection in a Murine Model

2021 ◽  
Vol 12 ◽  
Author(s):  
Mohammad Shahnaij ◽  
Mitsuhiro Iyori ◽  
Hiroaki Mizukami ◽  
Mayu Kajino ◽  
Iroha Yamagoshi ◽  
...  
Keyword(s):  
T Cells ◽  
Immune Responses ◽  
Malaria Vaccine ◽  
Infected Mosquito ◽  
Great Promise ◽  
Adeno Associated Virus ◽  
Boost Regimen ◽  
Cellular Immune Responses ◽  
Virus Serotype ◽  
Cellular Immune

Hepatocyte infection by malaria sporozoites is a bottleneck in the life-cycle of Plasmodium spp. including P. falciparum, which causes the most lethal form of malaria. Therefore, developing an effective vaccine capable of inducing the strong humoral and cellular immune responses necessary to block the pre-erythrocytic stage has potential to overcome the spatiotemporal hindrances pertaining to parasite biology and hepatic microanatomy. We recently showed that when combined with a human adenovirus type 5 (AdHu5)-priming vaccine, adeno-associated virus serotype 1 (AAV1) is a potent booster malaria vaccine vector capable of inducing strong and long-lasting protective immune responses in a rodent malaria model. Here, we evaluated the protective efficacy of a hepatotropic virus, adeno-associated virus serotype 8 (AAV8), as a booster vector because it can deliver a transgene potently and rapidly to the liver, the organ malaria sporozoites initially infect and multiply in following sporozoite injection by the bite of an infected mosquito. We first generated an AAV8-vectored vaccine expressing P. falciparum circumsporozoite protein (PfCSP). Intravenous (i.v.) administration of AAV8-PfCSP to mice initially primed with AdHu5-PfCSP resulted in a hepatocyte transduction rate ~2.5 times above that seen with intramuscular (i.m.) administration. This immunization regimen provided a better protection rate (100% sterile protection) than that of the i.m. AdHu5-prime/i.m. AAV8-boost regimen (60%, p < 0.05), i.m. AdHu5-prime/i.v. AAV1-boost (78%), or i.m. AdHu5-prime/i.m. AAV1-boost (80%) against challenge with transgenic PfCSP-expressing P. berghei sporozoites. Compared with the i.m. AdHu5-prime/i.v. AAV1-boost regimen, three other regimens induced higher levels of PfCSP-specific humoral immune responses. Importantly, a single i.v. dose of AAV8-PfCSP recruited CD8+ T cells, especially resident memory CD8+ T cells, in the liver. These data suggest that boost with i.v. AAV8-PfCSP can improve humoral and cellular immune responses in BALB/c mice. Therefore, this regimen holds great promise as a next-generation platform for the development of an effective malaria vaccine.

Immune Responses to Adeno-Associated Virus Vectors

2005 ◽  
Vol 5 (3) ◽  
pp. 323-331 ◽  
Author(s):  
Anne Zaiss ◽  
Daniel Muruve
Keyword(s):  
Immune Responses ◽  
Adeno Associated Virus ◽  
Virus Vectors

scholarly journals Cas9-specific immune responses compromise local and systemic AAV CRISPR therapy in multiple dystrophic canine models

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Chady H. Hakim ◽  
Sandeep R. P. Kumar ◽  
Dennis O. Pérez-López ◽  
Nalinda B. Wasala ◽  
Dong Zhang ◽  
...  
Keyword(s):  
Immune Responses ◽  
T Lymphocyte ◽  
Immune Suppression ◽  
Cytotoxic T Lymphocyte ◽  
Large Mammals ◽  
Treatment Results ◽  
Adeno Associated Virus ◽  
Muscle Inflammation ◽  
Canine Models ◽  
Therapy Treatment

AbstractAdeno-associated virus (AAV)-mediated CRISPR-Cas9 editing holds promise to treat many diseases. The immune response to bacterial-derived Cas9 has been speculated as a hurdle for AAV-CRISPR therapy. However, immunological consequences of AAV-mediated Cas9 expression have thus far not been thoroughly investigated in large mammals. We evaluate Cas9-specific immune responses in canine models of Duchenne muscular dystrophy (DMD) following intramuscular and intravenous AAV-CRISPR therapy. Treatment results initially in robust dystrophin restoration in affected dogs but also induces muscle inflammation, and Cas9-specific humoral and cytotoxic T-lymphocyte (CTL) responses that are not prevented by the muscle-specific promoter and transient prednisolone immune suppression. In normal dogs, AAV-mediated Cas9 expression induces similar, though milder, immune responses. In contrast, other therapeutic (micro-dystrophin and SERCA2a) and reporter (alkaline phosphatase, AP) vectors result in persistent expression without inducing muscle inflammation. Our results suggest Cas9 immunity may represent a critical barrier for AAV-CRISPR therapy in large mammals.

Assessment of Humoral, Innate, and T-Cell Immune Responses to Adeno-Associated Virus Vectors

2018 ◽  
Vol 29 (2) ◽  
pp. 86-95 ◽  
Author(s):  
Roberto Calcedo ◽  
Jessica A. Chichester ◽  
James M. Wilson
Keyword(s):  
T Cell ◽  
Immune Responses ◽  
Adeno Associated Virus ◽  
Virus Vectors ◽  
T Cell Immune Responses

scholarly journals Intraventricular Brain Injection of Adeno-Associated Virus Type 1 (AAV1) in Neonatal Mice Results in Complementary Patterns of Neuronal Transduction to AAV2 and Total Long-Term Correction of Storage Lesions in the Brains of β-Glucuronidase-Deficient Mice

2003 ◽  
Vol 77 (12) ◽  
pp. 7034-7040 ◽  
Author(s):  
Marco A. Passini ◽  
Deborah J. Watson ◽  
Charles H. Vite ◽  
Daniel J. Landsburg ◽  
Alyson L. Feigenbaum ◽  
...  
Keyword(s):  
Brain Structures ◽  
Adult Brain ◽  
Intraventricular Injection ◽  
Adeno Associated Virus ◽  
Neurometabolic Disorders ◽  
Virus Serotype ◽  
Neonatal Injection ◽  
Complete Reversal ◽  
The Brain ◽  
Deficient Mice

ABSTRACT Inherited metabolic disorders that affect the central nervous system typically result in pathology throughout the brain; thus, gene therapy strategies need to achieve widespread delivery. We previously found that although intraventricular injection of the neonatal mouse brain with adeno-associated virus serotype 2 (AAV2) results in dispersed gene delivery, many brain structures were poorly transduced. This limitation may be overcome by using different AAV serotypes because the capsid proteins use different cellular receptors for entry, which may allow enhanced global targeting of the brain. We tested this with AAV1 and AAV5 vectors. AAV5 showed very limited brain transduction after neonatal injection, even though it has different transduction patterns than AAV2 in adult brain injections. In contrast, AAV1 vectors, which have not been tested in the brain, showed robust widespread transduction. Complementary patterns of transduction between AAV1 and AAV2 were established and maintained in the adult brain after neonatal injection. In the majority of structures, AAV1 transduced many more cells than AAV2. Both vectors transduced mostly neurons, indicating that differential expression of receptors on the surfaces of neurons occurs in the developing brain. The number of cells positive for a vector-encoded secreted enzyme (β-glucuronidase) was notably greater and more widespread in AAV1-injected brains. A comprehensive analysis of AAV1-treated brains from β-glucuronidase-deficient mice (mucopolysaccharidosis type VII) showed complete reversal of pathology in all areas of the brain for at least 1 year, demonstrating that the combination of this serotype and experimental strategy is therapeutically effective for treating global neurometabolic disorders.

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