Limits...
Recombinant Adeno-Associated Virus-Mediated Expression of Methamphetamine Antibody Attenuates Methamphetamine-Induced Hyperactivity in Mice

View Article: PubMed Central - PubMed

ABSTRACT

Methamphetamine (Meth) is one of the most frequently abused drugs worldwide. Recent studies have indicated that antibodies with high affinity for Meth reduce its pharmacological effects. The purpose of this study was to develop a technique for virus-based passive immunization against Meth effects. We generated a recombinant adeno-associated virus serotype-8 vector (AAV-MethAb) carrying the gene for a Meth-specific monoclonal antibody (MethAb). Infection of 293 cells with AAV-MethAb resulted in the expression and secretion of antibodies which bind to Meth. The viral vector was then examined in adult ICR mice. Systemic administration of AAV-MethAb resulted in long-term expression of MethAb in the serum for up to 29 weeks. Serum collected from the animals receiving AAV-MethAb retained a high specificity for (+)-Meth. Animals were challenged with Meth five weeks after viral injection. Meth levels in the brain and serum were reduced while Meth-induced locomotor activity was significantly attenuated. In conclusion, AAV-MethAb administration effectively depletes Meth from brain and serum while reducing the behavioral response to Meth, and thus is a potential therapeutic approach for Meth abuse.

No MeSH data available.


Related in: MedlinePlus

AAV-MethAb infection induced long-lasting expression of MethAb in serum and reduced Meth levels in the brain and serum.(a) Mice were injected with AAV-MethAb (109 VGC/animal; n = 3, i.p.) or PBS (n = 4). Significant increases in MethAb expression in serum were found up to 29 weeks after AAV-MethAb injection (p < 0.0001, 2-way ANOVA; AAV-MethAb vs. PBS at 7, 17, 22, and 29 weeks post-injection). (b) Serum samples were pooled at 9 weeks after AAV-MethAb injection. Meth, but not other ligands, selectively competed with Meth-HRP for MethAb binding at a concentration of 10−5 mM. (c,d) At 15 weeks post-injection, all animals received Meth challenge (1 mg/kg, i.p.); brain and blood samples were collected 10 minutes later. The Meth concentrations in the brain and serum were significantly reduced (*p < 0.05, Student’s t-test) in AAV-MethAb injected mice.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC5384190&req=5

f2: AAV-MethAb infection induced long-lasting expression of MethAb in serum and reduced Meth levels in the brain and serum.(a) Mice were injected with AAV-MethAb (109 VGC/animal; n = 3, i.p.) or PBS (n = 4). Significant increases in MethAb expression in serum were found up to 29 weeks after AAV-MethAb injection (p < 0.0001, 2-way ANOVA; AAV-MethAb vs. PBS at 7, 17, 22, and 29 weeks post-injection). (b) Serum samples were pooled at 9 weeks after AAV-MethAb injection. Meth, but not other ligands, selectively competed with Meth-HRP for MethAb binding at a concentration of 10−5 mM. (c,d) At 15 weeks post-injection, all animals received Meth challenge (1 mg/kg, i.p.); brain and blood samples were collected 10 minutes later. The Meth concentrations in the brain and serum were significantly reduced (*p < 0.05, Student’s t-test) in AAV-MethAb injected mice.

Mentions: Adult male ICR mice (8 weeks) received AAV-MethAb (n = 3, at a dose of 109 VGC/animal, i.p.) or PBS (n = 4). Serum samples were collected before (0 weeks) and 2, 7, 17, 22, 29 weeks after virus injection (Fig. 2a). No anti-Meth antibody was found before the virus or PBS injection in week 0. In animals receiving AAV-MethAb, anti-Meth antibodies were first detected at 2 weeks, peaked (1.7 × 102 U/ml) at 7 weeks, and maintained at steady state to the last evaluated time point at the 29th week. These data suggest that a single intraperitoneal administration of AAV-MethAb resulted in a persistent long-term expression of anti-Meth antibodies in the peripheral blood.


Recombinant Adeno-Associated Virus-Mediated Expression of Methamphetamine Antibody Attenuates Methamphetamine-Induced Hyperactivity in Mice
AAV-MethAb infection induced long-lasting expression of MethAb in serum and reduced Meth levels in the brain and serum.(a) Mice were injected with AAV-MethAb (109 VGC/animal; n = 3, i.p.) or PBS (n = 4). Significant increases in MethAb expression in serum were found up to 29 weeks after AAV-MethAb injection (p < 0.0001, 2-way ANOVA; AAV-MethAb vs. PBS at 7, 17, 22, and 29 weeks post-injection). (b) Serum samples were pooled at 9 weeks after AAV-MethAb injection. Meth, but not other ligands, selectively competed with Meth-HRP for MethAb binding at a concentration of 10−5 mM. (c,d) At 15 weeks post-injection, all animals received Meth challenge (1 mg/kg, i.p.); brain and blood samples were collected 10 minutes later. The Meth concentrations in the brain and serum were significantly reduced (*p < 0.05, Student’s t-test) in AAV-MethAb injected mice.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5384190&req=5

f2: AAV-MethAb infection induced long-lasting expression of MethAb in serum and reduced Meth levels in the brain and serum.(a) Mice were injected with AAV-MethAb (109 VGC/animal; n = 3, i.p.) or PBS (n = 4). Significant increases in MethAb expression in serum were found up to 29 weeks after AAV-MethAb injection (p < 0.0001, 2-way ANOVA; AAV-MethAb vs. PBS at 7, 17, 22, and 29 weeks post-injection). (b) Serum samples were pooled at 9 weeks after AAV-MethAb injection. Meth, but not other ligands, selectively competed with Meth-HRP for MethAb binding at a concentration of 10−5 mM. (c,d) At 15 weeks post-injection, all animals received Meth challenge (1 mg/kg, i.p.); brain and blood samples were collected 10 minutes later. The Meth concentrations in the brain and serum were significantly reduced (*p < 0.05, Student’s t-test) in AAV-MethAb injected mice.
Mentions: Adult male ICR mice (8 weeks) received AAV-MethAb (n = 3, at a dose of 109 VGC/animal, i.p.) or PBS (n = 4). Serum samples were collected before (0 weeks) and 2, 7, 17, 22, 29 weeks after virus injection (Fig. 2a). No anti-Meth antibody was found before the virus or PBS injection in week 0. In animals receiving AAV-MethAb, anti-Meth antibodies were first detected at 2 weeks, peaked (1.7 × 102 U/ml) at 7 weeks, and maintained at steady state to the last evaluated time point at the 29th week. These data suggest that a single intraperitoneal administration of AAV-MethAb resulted in a persistent long-term expression of anti-Meth antibodies in the peripheral blood.

View Article: PubMed Central - PubMed

ABSTRACT

Methamphetamine (Meth) is one of the most frequently abused drugs worldwide. Recent studies have indicated that antibodies with high affinity for Meth reduce its pharmacological effects. The purpose of this study was to develop a technique for virus-based passive immunization against Meth effects. We generated a recombinant adeno-associated virus serotype-8 vector (AAV-MethAb) carrying the gene for a Meth-specific monoclonal antibody (MethAb). Infection of 293 cells with AAV-MethAb resulted in the expression and secretion of antibodies which bind to Meth. The viral vector was then examined in adult ICR mice. Systemic administration of AAV-MethAb resulted in long-term expression of MethAb in the serum for up to 29 weeks. Serum collected from the animals receiving AAV-MethAb retained a high specificity for (+)-Meth. Animals were challenged with Meth five weeks after viral injection. Meth levels in the brain and serum were reduced while Meth-induced locomotor activity was significantly attenuated. In conclusion, AAV-MethAb administration effectively depletes Meth from brain and serum while reducing the behavioral response to Meth, and thus is a potential therapeutic approach for Meth abuse.

No MeSH data available.


Related in: MedlinePlus