The question of whether a COVID-19 vaccine completely stops infection and transmission has been central since the first vaccines were introduced. Available vaccines are highly successful at preventing the worst outcomes of the disease, but they do not always prevent a person from becoming infected with SARS-CoV-2 or from passing it on. Immunity to a virus is not a single, all-or-nothing state, but rather a spectrum of protection. Understanding this spectrum requires distinguishing between two primary forms of immune defense: the kind that prevents any infection from taking hold, and the kind that prevents the infection from progressing into serious illness.
Defining Immunity: Sterilizing vs. Non-Sterilizing
The distinction between sterilizing and non-sterilizing immunity lies in where the immune system stops the viral attack. Sterilizing immunity is the complete blockage of a pathogen at its point of entry, preventing the virus from infecting cells, replicating, and establishing a foothold in the host. This form of defense eliminates the possibility of illness and stops the virus from being shed and transmitted to others. Achieving this requires a robust, localized defense at the body’s mucosal surfaces, such as the lining of the nose and throat.
Non-sterilizing immunity, which the current generation of injected COVID-19 vaccines primarily induces, prevents disease progression but not necessarily the initial infection. The virus gains entry to the body and begins to replicate, particularly in the upper respiratory tract. The systemic immune response rapidly detects the virus, neutralizing it before it can spread to the lungs or other organs. This quick clearance is highly effective at preventing severe illness and death, but because initial infection and some viral replication occur, transmission to others remains possible.
How Current COVID Vaccines Prevent Severe Disease
The current generation of COVID-19 vaccines, including the mRNA and viral vector platforms, are delivered via intramuscular injection. This route is specifically designed to elicit a strong systemic immune response. The vaccine components are taken up by cells in the muscle and nearby lymph nodes, initiating a body-wide defense that results in the production of circulating antibodies and T-cells.
The primary circulating antibodies are Immunoglobulin G (IgG), which flood the bloodstream and major tissues. These IgG antibodies are effective at neutralizing the SARS-CoV-2 virus once it enters the deeper parts of the body, such as the lungs, which is often involved in severe disease. Furthermore, the vaccines generate memory T-cells, including CD8+ cytotoxic T-cells. These specialized immune cells patrol the body, quickly identifying and destroying any cells that have already been infected by the virus. This limits the overall viral load and prevents the progression to critical illness, protecting vaccinated individuals from hospitalization and death.
The Role of Mucosal Immunity in Blocking Transmission
The SARS-CoV-2 virus begins its infection by attaching to and replicating in the epithelial cells that line the upper respiratory tract, particularly in the nose and throat. To achieve sterilizing immunity and block transmission, the immune system must neutralize the virus at this initial point of contact before it can infect the first cell. This requires a strong, localized defense known as mucosal immunity.
The most important component of this localized defense is Secretory Immunoglobulin A (sIgA), an antibody produced and secreted onto mucosal surfaces. A high concentration of sIgA in the nasal passages acts like a shield, trapping and neutralizing inhaled viral particles before they can bind to the host’s cells. Current injected vaccines are poor at generating this localized sIgA response because the vaccine is delivered far from the mucosal surfaces. This results in high levels of systemic IgG but only limited amounts of sIgA reaching the respiratory tract. The systemic immune response is activated too late to prevent the initial replication in the upper airways, which is sufficient for viral shedding and transmission.
Research Pathways for Sterilizing Vaccines
Acknowledging the limitations of injected vaccines in blocking transmission has prompted research toward developing vaccines that specifically target the mucosal immune system. This involves alternative delivery methods that introduce the vaccine directly to the respiratory tract. Intranasal spray vaccines, for example, are designed to stimulate the immune cells located in the nasal-associated lymphoid tissue (NALT).
By delivering the vaccine directly to the site of viral entry, these new formulations aim to induce the production of high levels of Secretory IgA. This localized stimulation is intended to create a firewall of antibodies on the mucosal surface, preventing the virus from gaining entry and achieving sterilizing immunity. Researchers are exploring various platforms for these mucosal vaccines, including live-attenuated and viral vector-based sprays, with several candidates having already entered clinical trials globally. The challenge remains in inducing a potent and long-lasting mucosal response, which is a complex immunological task, but achieving it would be a major advance in controlling the spread of respiratory viruses.