IgG IgA and sniffing a virus

Basic immunology 101, ignoring T memory cells and cell mediated immunity..

If you contract a respiratory virus it colonises your nose/throat/windpipe. If you are unlucky it will also colonise your lungs and you might well be headed for a week or two in the ITU.

If it doesn't, you get better.

If you are re exposed to the same virus a month later you will not become ill unless you have something very, very wrong with your immune system. But might you transmit the virus still?

You can track the response of your immune system to the virus by tracking serum antibody production. The immediate effect is to generate IgM antibodies. These fade after a few weeks and are used clinically as a marker for recent infection. After a week or so you make IgG antibodies. These are present for a few months or even for life, depending on which virus we are talking about and whether there is continued exposure. If they are "neutralising" antibodies they will actually stop the virus invading cells by attaching to the cell-invasion protein of the virus. They are protective against illness.

There is another class of "poor relation" antibodies, the IgAs. These are mucosal cell surface produced antibodies. They are produced on the membranes of your nose, throat, trachea and possibly lungs if the virus gets that far and you survive.

IgA largely stops the virus becoming re-established in your nose on re-exposure. Neither IgM nor IgG, even if it is a virus neutralising IgG antibody, is going to do this.

Just to avoid controversy (and because the paper is handy) let's look at mice vaccinated against influenza using an adenovirus vector vaccine. The group used exactly the same vaccine in two groups of mice, in one they gave it intranasally, in the other intramuscularly.

Reduction of influenza virus transmission from mice immunized against conserved viral antigens is influenced by route of immunization and choice of vaccine antigen

"Here we demonstrate that transmission reduction is more effective when mice are immunized against A/NP and M2 intranasally than via the intramuscular route"

The intranasal route stimulated marked IgA production. The intramuscular route produced a minimal IgA response. Once vaccinated the group then challenged the vaccinated mice with field virus and assessed the ability of those vaccinated mice to transmit the field virus to non protected mice.

Intranasal, IgA generating, vaccination reduced transmission by 88.2%.

There is nothing surprising about this.

I fully expected the same vaccine given intramuscularly to do nothing at all to reduce transmission but it did, oddly enough, reduce transmission potential by 47%. Of course the question to be asked is whether this 47% transmission rate reduction would allow a vaccinated care worker to safely nurse your granny during an influenza pandemic.

You also still have to ask whether an 88.2% reduction in transmission might make a care worker safe to nurse an elderly person.

An adenovirus vector vaccine will induced an immune response to the protein coded for in the mRNA built in to that vaccine. If injected in to a muscle it should induce IgG in the bloodstream to that protein which, if neutralising, should protect against illness. That's good, but limited.

Contrast that to a genuine field virus infection. It starts in your nose, spreads to your throat and then down your windpipe to give you a marked production of membrane based IgA throughout the airway. It is going to induce IgA production to a whole host of viral proteins, not just the one or two forms of IgGs generated by a vaccine (even if given intranasally to generate some IgA). Some field antibodies will be very useful, some less so.

It seems to me that the probability of reducing or even eliminating viral transmission might be much better from a field virus infection than from a limited antibody response generated by an vaccine, even if given intranasally.

Quite what might happen if you combined intranasal and intramuscular administration, or even gave two doses of intranasal vaccine a few weeks apart are open questions for mice in influenza models. Yes, a model is only a model.

How much of this might be generic to respiratory viruses in general I don't know but I would be amazed if it wasn't.

As always there are a slew of questions which follow on from this concept but I'll stop here with my fondness of IgA inducing vaccines and particularly of asymptomatic infections. Having said that, I would qualify it as a vet. Anyone who has had the pleasure of administering an intranasal vaccine to a 40kg aggressive dog who is voting against said intranasal vaccination with his teeth is another matter. Luckily you can get it in through a muzzle on a good day. 

Peter