I had indeed wondered why, as reported many years ago, humans sera contain natural antibodies with detectable in vitro activity against VSV, whereas sera from my naive mice never did. I am somewhat embarrassed to say I was unaware of the a-Gal differences amongst species.

It's interesting to note that many of us routinely grow VSV in Vero cells (African green monkey) which may lack a-Gal (do they come from OLD WORLD monkeys??), wheras other groups use BHKs which come from rodents and so definitely do not express a-Gal.

Perhaps raising lab mice in a (semi-)sterile environment also has an impact on their natural antibody repertoire?

Also, for those of us working in mouse models, it may be useful to consider the reverse scenario, ie do mice our mice make natural antibodies against antigens from the primate cells we may grow our viruses in? As I say I have not observed this but I have wondered whether mice mount an adaptive antibody response to Vero antigens when immunized with VSV grown in Veros.

Finally, as you mentioned, natural antibodies are generally complement-dependent and also very low titer, at least in the VSV example. It is not obvious to me why this should be the case if they are elicited by an adaptive response to bacterial antigens. Are these bacteria poorly immunogenic? Or do they antibodies just have very low avidity for the a-Gal in the context of a virus particle?

Thanks for a great virologist's virology post!