Original (antigenic) sin

(Second of two parts)

So, what is original antigenic sin?

When our immune system first encounters a foreign substance (an antigen), the existing antibodies (more correctly, the “immunoglobulins” found on the surface of certain immune cells, the so-called B cells) only have low affinity for the antigen. The B cells that are able to bind to the antigen are induced to proliferate; when they do, their immunoglobulins mutate and some of the daughter B cells are able to bind to the antigen with higher affinity. Those better-binding cells then have a decided advantage when the B cells are again induced to proliferate via antigen binding. After several cycles of this antigen binding-proliferation-selection process, the B cells that dominate are those which bind with high affinity for the antigen. Those B cells become transformed into antibody-secreting cells; some of those B cells become the memory cells against the antigen. Therein lies the cause of original antigenic sin.

Obviously, the memory B cells will be binding mostly to the immunodominant epitopes of the pathogen. When the pathogen mutates, the “old” antibodies are rendered no longer very effective (antibodies are very specific — they can distinguish between two proteins that differ by only one amino acid); there is a need to produce antibodies that are more specific for the “new” pathogen. If the pathogen maintains (most of) its immunodominant epitopes (and many pathogens are clever enough to do it), the memory B cells will dominate the immune response. The immune system will then continue to produce “old” antibodies, instead of antibodies that are more effective against the “new” pathogen. In so doing, our immune system, seduced by the evil pathogen, commits original antigenic sin.

But we are cleverer than the cleverest pathogens (since we have big brains and they have none, right?). Can we “wash away” original antigenic sin?

A number of researchers are trying to do that — including me. I have a paper in the Philippine Science Letters (http://www.philsciletters.org) wherein I outlined a strategy for coping with pathogens that are continually mutating, like the flu virus. A paper in the latest issue of the Philippine Journal of Science (Vol. 137, No. 1) presents the strategy in full detail. What I propose is a purely computational method for designing a vaccine in which the epitopes that were immunodominant are rendered less so. Such a vaccine will elicit an antibody response directed against more parts of the antigen and should not cause original antigenic sin — until the pathogen decides to have a major change (shift) in its (antigenic) structure that would cause us to sin again, which would then signal the need to design another vaccine.

Until we develop universal vaccines — ones that work regardless of any change in the structure of pathogens — we will probably keep getting the cold, the flu, etc., despite suffering from them many times before. Blame it on original (antigenic) sin.

* * *

Eduardo A. Padlan is a corresponding member of the NAST and is an adjunct professor in the Marine Science Institute, College of Science, University of the Philippines Diliman. He can be reached at [email protected].