The Pfizer-BioNTech and Moderna mRNA vaccines have played an important role in preventing deaths and serious infections from COVID-19. But researchers are still developing alternative approaches to vaccines to improve their effectiveness, including how they are administered. Immunologist and microbiologist Michael W. Russell from 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 protects the mucous surfaces of the body. These include the mouth, eyes, middle ear, mammary and other glands, as well as the gastrointestinal, respiratory and urogenital tracts. Antibodies and a variety of other antimicrobial proteins in the sticky secretions that coat these surfaces, as well as the immune cells located in the coating 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 internal tissues and organs. These circulating antibodies generally do not reach mucosal surfaces in large enough quantities to be effective. Thus, the mucosal and circulatory compartments of the immune system are largely separate and independent.
What are the key players in mucosal immunity?
The immune components that people are perhaps most familiar with are the 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 using additional proteins or immune cells.
The mucosal immune system generates a specialized form of antibody called Secretory IgA, or SIGA. Since SIgA is located in mucous secretions, such as saliva, tears, nasal and intestinal secretions, and breast milk, it is resistant to digestive enzymes that easily destroy other forms of antibodies. It is also superior to most other immunoglobulins in neutralizing viruses and toxins, and preventing bacteria from attaching to and invading cells lining the surface of organs.
There are also many other key players in the mucosal immune system, including different types of antimicrobial proteins that kill pathogens, as well as immune cells that generate antibody responses.
How does the COVID-19 virus enter the body?
Almost all infectious diseases in humans and other animals are acquired through mucosal surfaces, such as when eating or drinking, breathing, or through sexual contact. Major exceptions include wound infections or pathogens transmitted by insect or tick bites.
The virus that causes COVID-19, SARS-CoV-2, enters the body via droplets or aerosols that enter your nose, mouth or eyes. It can cause serious illness if it gets deep into the lungs and causes overactive and inflammatory immune response.
This means that the first contact of the virus with the immune system is likely 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, particularly 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 previous vaccination or infection, or occur quickly enough in response to a new infection, they could prevent serious illness by confining the virus to the upper respiratory tract until he is eliminated.
How do nasal vaccines work?
Vaccines can be administered mucosally through the mouth or the 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 orally. Currently, only one, the flu vaccine, is administered nasally.
In the case of nasal vaccines, viral antigens intended to stimulate the immune system would be taken up by immune cells in the lining of the nose or tonsils. Although the exact mechanisms by which nasal vaccines work in humans have not been thoroughly studied, researchers believe they act analogously to oral mucosal vaccines. The antigens contained in the vaccine induce the maturation of B lymphocytes in the mucosal sites into plasma cells which secrete a form of IgA. This IgA is then transported into mucous secretions throughout the body, where it becomes SIgA.
If SIgA antibodies in the nose, mouth or throat target SARS-CoV-2, they could neutralize the virus before it can fall into the lungs and establish an infection.
What advantage do mucosal vaccines have against COVID-19?
I think arguably the best way to protect an individual from COVID-19 is to block the virus at its point of entry, or at least confine it to the upper respiratory tract, where it could inflict relatively little damage.
Breaking the chains of viral transmission is crucial for controlling epidemics. Researchers know that COVID-19 is spreading during normal breathing and speaking, and is exacerbated by sneezing, coughing, shouting, singing, and other forms of exertion. Since these emissions come mainly from saliva and nasal secretions, where the predominant form of antibody present is SIgA, it stands to reason that secretions with a sufficiently high level of SIgA antibodies against the virus could neutralize each other and thereby reducing its transmissibility.
Existing vaccines, however, do not induce SIgA antibody responses. Injected vaccines mainly induce circulating IgG antibodies, which are effective in preventing serious lung disease. Nasal vaccines specifically induce SIgA antibodies in nasal and salivary secretions, where the virus is initially acquired, and may more effectively prevent transmission.
Nasal vaccines can be a useful complement to vaccines injected into foci of infection. Since they don’t require needles, they could also help overcome vaccine hesitancy due to fear of injections.
How close are researchers to creating a nasal COVID-19 vaccine?
There have been more than 100 oral or nasal COVID-19 vaccines in development around the world.
Most of them have been or are currently being tested in animal models. Many reported succeeded in inducing protective antibodies in blood and secretions, and prevented infection in these animals. However, few have been successfully tested in humans. Many have been abandoned without reporting all the details of the study.
According to World Health Organization14 COVID-19 nasal vaccines are in clinical trials at the end of 2022. Reports from China and India indicate that nasal or inhaled vaccines have been approved in these countries. But little information is publicly available about the results of studies supporting the approval of these vaccines.
This article is republished from The conversation, an independent non-profit news site dedicated to sharing ideas from academic experts. It was written by: Michael W. Russell, University at Buffalo. News from the experts, from an independent non-profit association. Try our free newsletters.
Michael W. Russell receives consulting fees from Therapyx, Inc. and has received previous (now inactive) research grants from the National Institutes of Health; he is also named on current grants from Therapyx, Inc. Therapyx has no interest in products for COVID-19.