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Wolfgang Miesbach: Adeno-Associated Virus Neutralizing Antibodies and Their Clinical Impact on Gene Therapy
Wolfgang Miesbach/LinkedIn
Apr 16, 2026, 09:41

Wolfgang Miesbach: Adeno-Associated Virus Neutralizing Antibodies and Their Clinical Impact on Gene Therapy

Wolfgang Miesbach, Professor of Medicine at Frankfurt University Hospital, shared a post on LinkedIn about a recent article by Rafael Parra et al, published in Gene Therapy:

”Pre-existing immunity to AAV vectors — are we underestimating the challenge for gene therapy eligibility?

The SAAVIA study (Parra  et al., Gene Therapy, 2026) provides some of the most comprehensive seroprevalence data to date from a healthy adult Spanish population (n=250):

IgG seroprevalence:

  • AAV6: 84% | AAV2: 74% | AAV8: 60% | AAV9: 51% | AAV5: 40%

Neutralizing antibodies (NAb):

  • AAV6: 63% | AAV8: 60% | AAV9: 52%

These NAb rates are substantially higher than those reported in most other developed countries (3–40%), and the co-seropositivity across serotypes reaches up to 97% for IgG and 83–91% for NAb – raising the possibility of broad cross-reactivity.

What makes this clinically relevant for haemophilia and gene therapy?

  • Even low NAb titers can completely abrogate AAV transduction. In most clinical trials, pre-existing NAb are a standard exclusion criterion — meaning a large proportion of otherwise eligible patients may never make it through screening.
  • The SAAVIA data suggest this challenge may be particularly pronounced in urban, high-mobility populations like Barcelona.

These findings take on added significance when placed alongside two landmark studies in the haemophilia field:

  • Klamroth et al. (2022, Hum Gene Ther) showed that AAV5 carries the lowest global seroprevalence (~35%) in people with haemophilia A across multiple countries – one reason AAV5 became the preferred vector for several haemophilia gene therapy programmes.
  • Klamroth et al. (2025, Mol Ther Methods Clin Dev) demonstrated that AAV5 NAb titers remain stable over 6 months in haemophilia B patients screened for etranacogene dezaparvovec – reassuring for trial logistics, but also a reminder that those with pre-existing immunity are consistently excluded.

Together, these three studies paint a clear picture: vector choice matters, regional seroprevalence matters, and standardized NAb testing across centers is needed.”

Title: Seroprevalence of anti-AAV antibodies in a healthy adult Spanish population: findings from the SAAVIA study

Authors: Rafael Parra, Assumpció Bosch, Angela Sánchez, Cristina Caparros, Hae Kyung Kim, Nadia Lwoff

Wolfgang Miesbach: Adeno-Associated Virus Neutralizing Antibodies and Their Clinical Impact on Gene Therapy

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AAV AAV Gene Therapy adeno-associated virus Angela Sánchez Assumpció Bosch Cristina Caparros Gene therapy Hae Kyung Kim haemophilia haemophilia A Haemophilia B Health Hematology Hemostasis Hemostasis News Hemostasis Today Medicine Nadia Lwoff Rafael Parra SAAVIA study thrombosis Wolfgang Miesbach
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