Complement and anti-alpha-galactosyl natural antibody-mediated inactivation of murine retrovirus occurs in adult serum but not in umbilical cord serum

Many retroviral vectors for hematopoietic cell and other clinical gene ther apy are derived from murine packaging cell lines. The exposure of these ret roviruses and packaging cell lines to adult human serum (AS) inactivates th em by complement and anti-alpha-galactosyl natural antibody-mediated mechan isms. We show that virus stability and infection efficiency of CRIP/BAG, a murine packaging cell line derived amphotropic retrovirus vector is reduced >95% following a 30-min incubation in AS. This inactivation is prevented b y replacing AS with umbilical cord serum (CS), wherein full retroviral tran sduction efficiency is maintained after 30 min of incubation. The loss of r etrovirus transduction efficiency in AS was smaller upon blockage of anti-a lpha-galactosyl antibodies with galactose alpha 1-3-galactose. Serum levels of CH 100, as well as Clq complement which inactivates retroviruses by an antibody-independent mechanism were similar in AS and CS. The high stabilit y of CRIP/BAG retrovirus vector in CS is likely due to its lower levels of maternally derived anti-alpha-galactosyl antibodies. These results have imp lications for in vivo gene transfer in adults and also in newborns sines ne onates do not produce natural antibodies during the initial months of life.