Circulating Antibodies and Macrophages as Modulators of Adenovirus Pharmacology

Diminished Innate Antiviral Response to Adenovirus Vectors in cGAS/STING-Deficient Mice Minimally Impacts Adaptive Immunity

“…Macrophages contribute directly to viral clearance (2)(3)(4). Virus uptake by these cells triggers an antiviral response through the activation of pattern recognition receptors (PRRs) (5)(6)(7)(8)(9).…”

Impact of Natural IgM Concentration on Gene Therapy with Adenovirus Type 5 Vectors

“…Natural IgM does not directly neutralize Ad5 in vitro (8), but natural IgM nevertheless inhibits liver transduction by Ad5 vectors in vivo (9,10). KCs are a major sink for Ad5 vectors (11)(12)(13)(14)(15).…”

“…Amounts of natural antibody differ among individual mice and between mouse strains (9,16). Although the presence of natural antibodies clearly inhibits Ad5 liver transduction (9,10), the impact of natural antibody concentrations is unclear.…”

“…Although the presence of natural antibodies clearly inhibits Ad5 liver transduction (9,10), the impact of natural antibody concentrations is unclear. To examine ;CD19 cre/ϩ mice have a B cell-specific deletion in the Shp1 tyrosine phosphatase which causes expansion of B-1a cells and elevated IgM (24).…”

“…Error bars represent SD. Transferring natural IgM to antibody-deficient mice decreases Ad5 liver transduction, while transfer of natural IgG has no effect (9,10). Recently, Unzu et al (10) found that liver transduction was suppressed by transfer of a monoclonal IgM antibody against the human AE2 anion exchanger, suggesting that IgM may nonspecifically suppress liver transduction by Ad5.…”