MR-guided parenchymal delivery of adeno-associated viral vector serotype 5 in non-human primate brain

One potential setback to the use of gene therapy for the treatment of Sjögren’s syndrome is the presence of neutralizing antibodies (nAb) against adeno-associated virus (AAV) serotypes. In order to evaluate the efficacy of this treatment option, nAb titers were measured in both healthy individuals and Sjögren’s patients. Several serotypes with known transduction activity in mouse salivary glands were tested and only AAV5 showed a statistically significant change in the prevalence of nAbs between Sjögren’s and healthy participants. Both groups showed a higher rate of nAbs for AAV2 compared with most of the other serotypes tested, except for bovine AAV (BAAV). Although a similar rate of seropositivity was seen against BAAV and AAV2, the percentage of samples with high titer was significantly lower with BAAV. Furthermore, the majority of positive samples exhibited low nAb titers in the primary Sjögren’s syndrome (pSS) group for all serotypes except for AAV2. AAV5 was the only serotype that showed a statistically significant shift in the percentage of medium or high neutralizing titer. Based on these results, many serotypes are viable vectors in a gene therapy approach and pSS patients do not have a statistically significant higher rate of seropositivity or titer compared with healthy donors.

• Publication year

  2017

• Venue

  Gene Therapy

• Publication date

  2017-02-02

• Fields of study

  Biology, Medicine, Engineering

• Identifiers
  DOI 10.1038/gt.2017.1PMID 28300083PMCID 5404203
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• Primary Sjögren’s syndrome patients did not show a statistically significant increase in seropositivity or neutralizing antibody titer compared with healthy donors across the tested serotypes.

  Confidence 0.96

  박진우 (dztg5apj7m) extraction뀨 (7c402c1b98) reviewKiller Whale (322360f1c1) reviewB (s683577b42) review
• Neutralizing antibody rates were higher for AAV2 than for most of the other tested serotypes in both groups, while bovine AAV showed a similar seropositivity rate but a lower proportion of high-titer samples than AAV2.

  Confidence 0.94

  박진우 (dztg5apj7m) extraction뀨 (7c402c1b98) reviewKiller Whale (322360f1c1) reviewB (s683577b42) review
• AAV5 was the only serotype that showed a statistically significant difference in neutralizing antibody prevalence between primary Sjögren’s syndrome patients and healthy participants.

  Confidence 0.97

  박진우 (dztg5apj7m) extraction뀨 (7c402c1b98) reviewKiller Whale (322360f1c1) reviewB (s683577b42) review

• aav2

  virus variant, biological entity

  The adeno-associated virus serotype 2 capsid variant evaluated alongside other serotypes for neutralizing antibody prevalence and titer.

  Aliases: adeno-associated virus serotype 2

  박진우 (dztg5apj7m) extraction뀨 (7c402c1b98) reviewKiller Whale (322360f1c1) reviewB (s683577b42) review
• aav5

  virus variant, biological entity

  The adeno-associated virus serotype 5 capsid variant included among the serotypes evaluated for neutralizing antibodies.

  Aliases: adeno-associated virus serotype 5

  박진우 (dztg5apj7m) extraction뀨 (7c402c1b98) reviewKiller Whale (322360f1c1) reviewB (s683577b42) review
• adeno-associated virus serotypes

  virus variants, biological entities

  The different AAV capsid variants tested for serum antibody prevalence in the healthy and primary Sjögren’s syndrome groups.

  Aliases: AAV serotypes

  박진우 (dztg5apj7m) extraction뀨 (7c402c1b98) reviewKiller Whale (322360f1c1) reviewB (s683577b42) review
• bovine aav

  virus variant, biological entity

  A bovine adeno-associated virus serotype included in the serologic comparison against human participant sera.

  Aliases: BAAV

  박진우 (dztg5apj7m) extraction뀨 (7c402c1b98) reviewKiller Whale (322360f1c1) reviewB (s683577b42) review
• gene therapy

  therapeutic approach

  A therapeutic strategy discussed as the application context for using adeno-associated viral vectors in Sjögren’s syndrome.

  박진우 (dztg5apj7m) extraction뀨 (7c402c1b98) reviewKiller Whale (322360f1c1) reviewB (s683577b42) review
• neutralizing antibodies

  measurement, immune response

  Antibodies in serum that block adeno-associated virus infection or transduction and were measured as titers in the participant samples.

  Aliases: nAb, nAbs

  박진우 (dztg5apj7m) extraction뀨 (7c402c1b98) reviewKiller Whale (322360f1c1) reviewB (s683577b42) review
• primary sjögren’s syndrome

  condition, disease group

  The autoimmune patient group compared with healthy donors for adeno-associated virus neutralizing antibody prevalence and titer.

  Aliases: pSS, Sjögren’s syndrome

  박진우 (dztg5apj7m) extraction뀨 (7c402c1b98) reviewKiller Whale (322360f1c1) reviewB (s683577b42) review

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