When we generally speak of the immune response to viral infections, we talk of neutralising antibodies. These are antibodies that can neutralise the effect of the virus and reduce its load.

My question is, what do the rest of the antibodies produced, which are not neutralising, even do?

Is it a failure of the immune response of the body to produce antibodies that are not neutralising? But isn't binding enough for opsonisation?

How is 'neutralising' even defined? Are such antibodies neutralising just based on binding (since I assume neutralisation assays are in-vitro) or do even these antibodies require downstream antibody effector mechanisms like complement, opsonisation, ADCC etc. for neutralisation?

  • $\begingroup$ Which antibodies do you mean with "not neutralizing"? The ones which are generated in the process of making highly specific antibodies in the process which do not fit or the majority of antibodies which are always present in the circulation? $\endgroup$ – Chris Aug 13 '16 at 13:16
  • $\begingroup$ @Chris I dont know. I just assumed that if some antibodies are called neutralising antibodies, the others must be non-neutralising. I know, not a safe assumption, but still... $\endgroup$ – Polisetty Aug 13 '16 at 13:27
  • $\begingroup$ Ok , what is your knowledge about antibody maturation? $\endgroup$ – Chris Aug 13 '16 at 13:28
  • $\begingroup$ @Chris I know that the activated B-cell undergoes somatic hypermutation in the germinal centre, followed by selection of better ones by FDCs $\endgroup$ – Polisetty Aug 13 '16 at 13:50

The term "neutralizing" depends on context. In virology, it generally (not always) means it prevents the virus from binding to its receptor(s) and getting its genetic material inside the now-infected cell. Other antibodies can bind other epitopes besides the sites of binding between capsid and receptor (or enveloping membrane and receptor), yet still contribute to the immune response. Such antibodies are often opsonizing. Still more antibodies are just ineffective, a byproduct of the antibody maturation process.

  • $\begingroup$ Are there neutralising antibodies elsewhere? I mean, in a context other than virology? $\endgroup$ – Polisetty Aug 14 '16 at 5:52
  • $\begingroup$ @Polisetty sure. One example is in enzyme replacement therapy, where patients genetically lacking an enzyme in a metabolic pathway can have it replaced by injecting recombinant protein into the bloodstream. These proteins have a certain glycosylation pattern, such as high levels of terminal mannose-6-phosphate residues, and they bind the M6P receptor on target cells and are internalized. Since the injected protein is foreign to the patient's immune system, they can raise a variety of antibody responses against it. A neutralizing antibody could bind to the protein's active site, for example, $\endgroup$ – MattDMo Aug 15 '16 at 21:25
  • $\begingroup$ and prevent the enzyme from catalyzing its reaction. Another response, which is sometimes called neutralizing, has antibodies binding the M6P residues and preventing the protein from binding the M6P receptor. You can read about other neutralizing responses here. Typically they are discussed in the context of virology, but the diphtheria antitoxin antibody response is another good example of a non-viral response. $\endgroup$ – MattDMo Aug 15 '16 at 21:30

"Neutralizing" is not a general concept; it's context-dependent. Most often (in virology anyway) it means that the antibodies, by themselves in a tissue culture plate, can prevent infection of the cells by the virus. Many antibodies that are "non-neutralizing" in tissue culture are probably protective in the animal, in the context of complement and phagocytic cells and so on.

That said, there's no reason why antibodies should be protective, let alone neutralizing. Antibodies don't arise in a guided manner with foreknowledge; antibody development is driven by physical interactions between the antibody and its binding partner. If they happen to arise to something irrelevant -- an internal protein of a virus, or a pollen grain, perhaps -- then they can still be driven through priming and development and maturation and still be functionally useless, or even harmful.

On top of that, of course it would be beneficial for pathogens to be resistant to antibodies, and at least a few have evolved this ability, so for those pathogens many antibodies would be non-neutralizing and non-protective.


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