Can a protein recognized by antibodies not be immunogenic?

Can a protein recognized by antibodies not be immunogenic?

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I have a protein that is produced with the baculovirus system that is recognized by antibodies generated by immunization of rabbits with the same protein produced in E. coli. However the baculovirus protein did not induce an antibody response when I immunized some pigs.

Could it be that the baculovirus protein is not immunogenic? Even if the same protein is recognized by antibodies? If the rabbits produced antibodies with a protein that did not have post-translational modifications, how can not be immunogenic when the modifications are added?

Pure proteins are often poorly immunogenic because you need to have some kind of "adjuvant" effect to induce a strong effect. Bacterially-produced proteins may well have some bacterial LPS or other immune stimulants still present after purification which would drive a much stronger response than the same protein produced from eukaryotic cells. There are many other possible explanations -- one or the other protein may have aggregated or misfolded, which could drive a different response, for example.

In other words the effect you're seeing may be annoying but is not particularly shocking, and you have no choice but to do some routine troubleshooting at this point. Is your protein more immunogenic when administered with an adjuvant? Are the two versions identically folded? Are there antibodies present to a misfolded form that you're not detecting? And so on.


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