The IGA immune system comprises approximately 2/3 of all the immune cells in the body. Intestinal tract, respiratory tract, and skin are all exterior surfaces and are required to hold the environments’ many pathogens at bay.

IGA is one of several classes of immunoglobulins, the others being Gamma M, Gamma E, and several sub classes of Gamma G. They each have different structures and functions, but all have the basic underlying mechanisms of antigen presentation, clonal expansion, heavy chain and light chain dimers and specificity.

Mucosal gamma A occurs in pairs, with a junctional J chain and a secretory piece; The latter serves as a type of receptor on the cell surface; Imagine millions of gamma A combining sites waving on the surface of respiratory and intestinal epithelium waiting for pathogens to come along. Once combined with the virus or bacterium, they are shed into the mucus and eliminated before the virus can get to the mucosal cells.

With an IM injection of COVID-19 vaccine, all of the immunoglobulin classes except for Gamma E respond, with the earliest anybody at four or five days and peaking at 11 to 12 days. Gamma A  in the serum occurs as a single antibody, as opposed to the secretory IGA which occur in pairs. Gamma G and M reside in the serum, and do not occur in any significant amounts in the mucus, leaving  secretory gamma A alone to directly face the outside world.

Nasal immunization should theoretically be the route of choice for respiratory viruses. There is a vigorous response not only in the production of mucosal secretory IGA, but also in the production of serum immunoglobulins including IgG. However, the Titanic of medical practice turns very slowly. Part of the problem is probably tradition; immunizations have always been given by subcutaneous or intramuscular injection.

When a substance is injected, you know that it’s in the body in a precise amount, the tissues are very vascular, and the pick up rate is known, and it works well. With IM immunizations, people may get sick, because the lining membranes are not protected, but the immunized person rapidly produces huge amounts of IgG which usually keeps the infection under control. Covid is unique in its ability to evade the innate immune system, and multiply rapidly before the humoral immune response is adequate. Also, Covid  Immunity wanes rapidly, aided by the fact that Covid is always changing it’s outer form.

There are more than a dozen nasal Covid vaccines being investigated, and the early studies on hamsters and mice showed a robust mucosal antibody production as well as a serum IgG production at least as great as intramuscular injection.

There are, however, several problems. An attenuated, live COVID-19 vaccine would theoretically be the best, since the virus itself is able to get into the cells and start replicating. However, lack of experience makes the medical profession fearful. There are a huge number of “do not give to” warnings on the only currently approved nasal vaccine, which is an attenuated influenza virus. There are worries about immunodeficient people, older people, pregnant people and about the possibility that the attenuated virus will go into the central nervous system via the olfactory system.

There are practical concerns as well. Viral vector vaccines may stimulate an amnestic response to the vector that excludes the vaccine from entering the cells. The nasal vaccine might be swept away with the mucus. How much is the vaccine will remain in the nasal tissues? Will patients have any confidence in the vaccine since it’s just a spray in the nose? Will it be abused, since literally anybody could administer the nasal vaccine.

The bottom line is that of the many vaccines in trial, not a single one is expected to be approved until the early fall. Interestingly, Pfizer is working with an mRNA nasal vaccine. DNA nasal vaccines are also being tried, since DNA is a more stable molecule. A number of adenoviral vectored vaccines are in trials.

The nasal route for immunization is so promising that I believe we will eventually have nasal vaccines, hopefully tailored for current viral variants.

Nasal antibody administration, or a small molecule drug that will combine with Covid are being looked at, but since they do not produce more than transient effects, I doubt if they will be very popular. Carrageenan is an approved substance that ties up viruses, and might have a chance to succeed as a nasal spray treatment.

Pills are so much for more familiar to people as a treatment device, and seem more attractive to drug companies. I do not believe that nasal sprays will replace them as the staple of outpatient medical treatment.

—Dr. C.