UNASSIGNED: Adeno-associated virus serotype 1 ( @entity21481 ) has many advantages as a gene therapy vector, but the presence of pre-existing neutralizing antibodies (NAbs) is an important limitation. This study was designed to determine: (1) characteristics of AAV NAbs in @entity1 subjects, (2) prevalence of @entity21481 NAbs in @entity712 @entity1 and (3) utility of aggressive immunosuppressive therapy in reducing NAb seroconversion in an animal model. NAb titers were assessed in a cohort of @entity712 @entity1 and in @entity1 screened for a clinical trial of gene therapy with @entity21481 carrying the sarcoplasmic reticulum @entity460 ATPase gene ( @entity21481 /SERCA2a). @entity21481 NAbs were found in 59.5% of 1552 @entity712 @entity1 . NAb prevalence increased with age (P=0.001) and varied geographically. The pattern of NAb titers suggested that exposure is against @entity4700 , with @entity21481 NAb seropositivity due to crossreactivity. The effects of immunosuppression on NAb formation were tested in mini- @entity1707 treated with immunosuppressant therapy before, during and after a single @entity21481 /SERCA2a infusion. Aggressive immunosuppression did not prevent formation of @entity21481 NAbs. We conclude that immunosuppression is unlikely to be a viable solution for repeat @entity21481 dosing. Strategies to reduce NAbs in @entity712 @entity1 are needed to increase eligibility for gene transfer using AAV vectors.Gene Therapy advance online publication, 24 December 2015; doi:10.1038/gt.2015.109.

Prevalence of AAV1 neutralizing antibodies and consequences for a clinical trial of gene transfer for advanced XXXX .

@entity1 :: ('9606', 'Species') :: ['human', 'patients'] @entity1707 :: ('9823', 'Species') :: ['pigs'] @entity712 :: ('MESH:D006333', 'Disease') :: ['heart failure'] @entity460 :: ('MESH:D002118', 'Chemical') :: ['calcium'] @entity4700 :: ('10804', 'Species') :: ['AAV2'] @entity21481 :: ('57579', 'Species') :: ['AAV1']
@entity712 :: (MESH:D006333,Disease) :: ['heart failure']
