Intranasal COVID vaccines are administered as a spray delivered directly into the nose, unlike traditional intramuscular injections. These needle-free formulations induce immunity at the respiratory tract, the primary entry point for the SARS-CoV-2 virus. While injectable vaccines primarily prevent severe disease, nasal delivery aims to improve protection and potentially block infection completely. This approach may offer distinct public health advantages over established vaccines.
How Intranasal Vaccines Activate Mucosal Immunity
The core difference between injectable and intranasal vaccines is the immune response generated. Injectable vaccines create a systemic response, generating Immunoglobulin G (IgG) antibodies that circulate in the bloodstream to prevent severe illness. Intranasal vaccines stimulate the mucosal immune system, which lines the respiratory and gastrointestinal tracts where the virus first lands.
This mucosal stimulation produces Immunoglobulin A (IgA) antibodies, the predominant antibody found in secretions like mucus, saliva, and tears. Secretory IgA coats the mucous membranes of the nose and throat to neutralize the virus upon exposure. By neutralizing the virus before it can infect host cells, the nasal vaccine aims for sterilizing immunity, preventing infection itself.
IgA antibodies are structurally more effective at viral neutralization at mucosal surfaces than circulating IgG antibodies. IgA’s dimeric structure, consisting of two linked antibody units, gives it four binding sites. This structure makes IgA more resistant to viral mutations and cross-reactive against different variants. This localized immune reaction targets the site where the SARS-CoV-2 virus initiates infection and shedding.
Distinct Advantages of Targeting the Respiratory Tract
Intranasal vaccines offer several practical benefits for individuals and public health. The most significant advantage is the reduction of viral transmission. By clearing the virus rapidly from the nasal passages, where viral load is highest, these vaccines minimize the chance that a vaccinated individual will pass the virus to others, a feature injectable vaccines were less effective at providing.
The needle-free application addresses vaccine hesitancy related to needle phobia and simplifies the vaccination process. The ease of administration via a simple nasal spray could also allow for future self-administration, increasing compliance and simplifying mass vaccination campaigns.
Because the immune response is localized to the respiratory tract, intranasal vaccines may result in fewer systemic side effects, such as fever, fatigue, and muscle aches, compared to traditional intramuscular shots. This direct targeting matches the virus’s natural route of infection, leading to a quicker immune response and a more effective barrier against initial viral colonization.
Current State of Global Research and Approval
Intranasal COVID vaccines have progressed through the standard phases of clinical trials (Phase I for safety, Phase II for immune response, and Phase III for efficacy). Regulatory hurdles for these mucosal vaccines require data demonstrating mucosal immune activation, such as IgA presence in nasal lavage fluid. This process has taken longer than the emergency approval of first-generation injectable vaccines.
Despite these challenges, several countries have authorized intranasal COVID vaccines for use. India, for example, authorized the iNCOVACC vaccine, a viral vector-based nasal spray, in September 2022. China authorized several versions, including the inhaled viral vector vaccine Convidecia and the intranasal Pneucolin. Russia also authorized an intranasal version of the Sputnik vaccine.
In Western regulatory bodies, such as the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA), many intranasal candidates remain in various stages of clinical investigation. Widespread availability of a fully approved intranasal option in North America and Europe is contingent on the completion of large-scale clinical trials proving efficacy and safety.