The Pfizer-BioNTech and Moderna mRNA vaccines have performed a big position in stopping deaths and extreme infections from COVID-19. But researchers are still in the process of developing alternative approaches to vaccines to improve their effectiveness, including how they’re administered. Immunologist and microbiologist Michael W. Russell of the University at Buffalo explains how nasal vaccines work, and where they are in the development pipeline.
How does the immune system fight pathogens?
The immune system has two distinct components: mucosal and circulatory.
The mucosal immune system provides protection at the mucosal surfaces of the body. These include the mouth, eyes, middle ear, the mammary and other glands, and the gastrointestinal, respiratory, and urogenital tracts. Antibodies and a variety of other anti-microbial proteins in the sticky secretions that cover these surfaces, as well as immune cells located in the lining of these surfaces, directly attack invading pathogens.
The circulatory part of the immune system generates antibodies and immune cells that are delivered through the bloodstream to the internal tissues and organs. These circulating antibodies do not usually reach the mucosal surfaces in large enough amounts to be effective. Thus mucosal and circulatory compartments of the immune system are largely separate and independent.
What are the key players in mucosal immunity?
The immune components people may be most familiar with are proteins known as antibodies, or immunoglobulins. The immune system generates antibodies in response to invading agents that the body identifies as “non-self,” such as viruses and bacteria.
Antibodies bind to specific antigens: the part or product of a pathogen that induces an immune response. Binding to antigens allows antibodies to either inactivate them, as they do with toxins and viruses, or kill bacteria with the help of additional immune proteins or cells.
The mucosal immune system generates a specialized form of antibody called secretory IgA, or SIgA. Because SIgA is located in mucosal secretions, such as saliva, tears, nasal and intestinal secretions, and breast milk, it is resistant to digestive enzymes that readily destroy other forms of antibodies. It is also superior to most other immunoglobulins at neutralizing viruses and toxins, and at preventing bacteria from attaching to and invading the cells lining the surfaces of organs.
There are also many other key players in the mucosal immune system, including different types of anti-microbial proteins that kill pathogens, as well as immune cells that generate antibody responses.
Mucus is among the central secretions of the mucosal immune system.
How does the COVID-19 virus enter the physique?
Nearly all infectious ailments in individuals and different animals are acquired through mucosal surfaces, equivalent to by consuming or ingesting, respiratory or sexual contact. Main exceptions embody infections from wounds, or pathogens delivered by insect or tick bites.
The virus that causes COVID-19, SARS-CoV-2, enters the body via droplets or aerosols that get into your nose, mouth, or eyes. It can cause severe disease if it descends deep into the lungs and causes an overactive, inflammatory immune response.
This means that the virus’s first contact with the immune system is probably through the surfaces of the nose, mouth, and throat. This is supported by the presence of SIgA antibodies against SARS-CoV-2 in the secretions of infected people, including their saliva, nasal fluid, and tears. These locations, especially the tonsils, have specialized areas that specifically trigger mucosal immune responses.
Some research suggests that if these SIgA antibody responses form as a result of vaccination or prior infection, or occur quickly enough in response to a new infection, they could prevent serious disease by confining the virus to the upper respiratory tract until it is eliminated.
How do nasal vaccines work?
Vaccines can be given through mucosal routes via the mouth or nose. This induces an immune response through areas that stimulate the mucosal immune system, leading mucosal secretions to produce SIgA antibodies.
There are several existing mucosal vaccines, most of them taken by mouth. Currently, only one, the flu vaccine, is delivered nasally.
In the case of nasal vaccines, the viral antigens intended to stimulate the immune system would be taken up by immune cells within the lining of the nose or tonsils. While the exact mechanisms by which nasal vaccines work in people have not been thoroughly studied, researchers believe they work analogously to oral mucosal vaccines. Antigens in the vaccine induce B cells in mucosal sites to mature into plasma cells that secrete a form of IgA. That IgA is then transported into mucosal secretions throughout the body, where it becomes SIgA.
If the SIgA antibodies in the nose, mouth or throat target SARS-CoV-2, they could neutralize the virus before it can drop down into the lungs and establish an infection.
Nasal vaccines might present a extra approachable various to injections for sufferers leery of needles.
What benefit do mucosal vaccines have in opposition to COVID-19?
I consider that arguably the easiest way to guard a person in opposition to COVID-19 is to dam the virus at its level of entry, or at the least to restrict it to the higher respiratory tract, the place it’d inflict comparatively little injury.
Breaking chains of viral transmission is essential to controlling epidemics. Researchers know that COVID-19 spreads throughout regular respiratory and speech, and is exacerbated by sneezing, coughing, shouting, singing and different types of exertion. As a result of these emissions principally originate from saliva and nasal secretions, the place the predominant type of antibody current is SIgA, it stands to purpose that secretions with a sufficiently excessive stage of SIgA antibodies in opposition to the virus might neutralize and thereby diminish its transmissibility.
Existing vaccines, nevertheless, don’t induce SIgA antibody responses. Injected vaccines primarily induce circulating IgG antibodies, that are efficient in stopping severe illness within the lungs. Nasal vaccines particularly induce SIgA antibodies in nasal and salivary secretions, the place the virus is initially acquired, and may extra successfully forestall transmission.
Nasal vaccines could also be a helpful complement to injected vaccines in sizzling spots of an infection. Since they don’t require needles, they may additionally assist overcome vaccine hesitancy resulting from fear of injections.
How shut are researchers to making a nasal COVID-19 vaccine?
There have been over 100 oral or nasal COVID-19 vaccines in development world wide.
Most of those have been or are at the moment being examined in animal fashions. Many have reported efficiently inducing protecting antibodies within the blood and secretions, and have prevented an infection in these animals. Nevertheless, few have been efficiently examined in individuals. Many have been abandoned with out absolutely reporting research particulars.
In accordance with the World Health Organization, 14 nasal COVID-19 vaccines are in scientific trials as of late 2022. Stories from China and India point out that nasal or inhaled vaccines have been permitted in these international locations. However little data is publicly obtainable concerning the outcomes of the research supporting approval of those vaccines.
Written by Michael W. Russell, Professor Emeritus of Microbiology and Immunology, College at Buffalo.
This text was first printed in The Conversation.