Anti-adeno-associated virus serotype 8 neutralizing antibody (Anti-AAV8 NAb) (Anti-AAV8 NAb)

Anti-adeno-associated virus serotype 8 (AAV8) neutralizing antibodies are host-produced immunoglobulins, primarily of the IgG class, that recognize and bind to the AAV8 viral capsid (Boutin et al., 2010, Gene Therapy). These antibodies function by preventing the viral vector from attaching to or entering target cells, thereby neutralizing its ability to deliver therapeutic genetic material. While AAV8 is a preferred vector for liver-directed gene therapy due to its high tropism, pre-existing immunity is a major clinical hurdle, with prevalence rates in the human population ranging from 15% to over 40% (Calcedo et al., 2009, Journal of Infectious Diseases). These antibodies are often cross-reactive, meaning they can be triggered by exposure to other AAV serotypes but still neutralize AAV8 due to conserved capsid epitopes (Louis Jeune et al., 2013, Human Gene Therapy Methods). In clinical practice, drugs like Imlifidase are being investigated to enzymatically cleave these antibodies, creating a temporary window for successful vector administration (Leborgne et al., 2020, Nature Medicine). Other strategies include plasmapheresis to physically remove the antibodies or the use of immunosuppressants to prevent their formation or rebound. Managing these antibodies is critical for patient eligibility and the overall success of systemic gene delivery (Mingozzi & High, 2013, Nature Reviews Genetics).

Other names

AAV8 neutralizing antibodiesAnti-AAV8 NAbsPre-existing AAV8 antibodiesCross-reactive AAV8 antibodiesAnti-AAV8 IgG

Therapeutic strategies involve the enzymatic cleavage of IgG antibodies, physical removal via plasmapheresis, or the depletion of antibody-producing B-cells and plasma cells to allow successful viral vector transduction.