Pre-existing anti-adenovirus type 5 neutralizing antibodies (Anti-Ad5 NAb)

Pre-existing anti-adenovirus type 5 (Ad5) neutralizing antibodies (NAbs) are host-produced immunoglobulins that arise from natural exposure to the common human adenovirus serotype 5 (PubMed: 21148215). These antibodies specifically recognize and bind to the Ad5 capsid proteins, including the hexon, penton base, and fiber, which are critical for the virus's ability to infect host cells (NIH: PMC7454311). In the field of biotherapeutics, these NAbs act as a significant barrier to the efficacy of Ad5-vectored vaccines and gene therapies by neutralizing the vector before it can deliver its genetic payload to the target cells (Nature: 10.1038/s41541-020-0171-6). This pre-existing immunity is widespread in the human population, with seroprevalence rates exceeding 90% in some geographic regions, which can lead to highly variable clinical outcomes (The Lancet: 10.1016/S0140-6736(20)31208-3). To address this challenge, researchers often screen patients for NAb titers or utilize alternative viral vectors, such as those derived from rare human serotypes or non-human species, to bypass the inhibitory effects of these antibodies. Furthermore, high levels of these antibodies can sometimes lead to an increased risk of adverse immune reactions if high doses of the vector are administered to overcome the neutralization. The presence of these antibodies was a key factor in the failure of the STEP HIV vaccine trial, highlighting their importance in clinical trial design (PubMed: 18996973).

Other names

Anti-Ad5 antibodiesAdenovirus type 5 neutralizing antibodiesPre-existing immunity to Ad5Ad5-specific NAbsAnti-Ad5 humoral immunity

Neutralization of viral vectors by binding to capsid proteins (hexon, penton, fiber), thereby preventing cell entry and transgene delivery.